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Abstract Background High-frequency transcutaneous neuromuscular electrical nerve stimulation (TENS) is currently used for the administration of electrical current in denervated muscle to alleviate muscle atrophy and enhance motor function; however, the time window (i.e. either immediate or delayed) for achieving benefit is still undetermined. In this study, we conducted an intervention of sciatic nerve crush injury using high-frequency TENS at different time points to assess the effect of motor and sensory functional recovery. Results Animals with left sciatic nerve crush injury received TENS treatment starting immediately after injury or 1 week later at a high frequency(100 Hz) or at a low frequency (2 Hz) as a control. In SFI gait analysis, either immediate or late admission of high-frequency electrical stimulation exerted significant improvement compared to either immediate or late administration of low-frequency electrical stimulation. In an assessment of allodynia, immediate high frequency electrical stimulation caused a significantly decreased pain threshold compared to late high-frequency or low-frequency stimulation at immediate or late time points. Immunohistochemistry staining and western blot analysis of S-100 and NF-200 demonstrated that both immediate and late high frequency electrical stimulation showed a similar effect; however the effect was superior to that achieved with low frequency stimulation. Immediate high frequency electrical stimulation resulted in significant expression of TNF-α and synaptophysin in the dorsal root ganglion, somatosensory cortex, and hippocampus compared to late electrical stimulation, and this trend paralleled the observed effect on somatosensory evoked potential. The CatWalk gait analysis also showed that immediate electrical stimulation led to a significantly high regularity index. In primary dorsal root ganglion cells culture, high-frequency electrical stimulation also exerted a significant increase in expression of TNF-α, synaptophysin, and NGF in accordance with the in vivo results. Conclusion Immediate or late transcutaneous high-frequency electrical stimulation exhibited the potential to stimulate the motor nerve regeneration. However, immediate electrical stimulation had a predilection to develop neuropathic pain. A delay in TENS initiation appears to be a reasonable approach for nerve repair and provides the appropriate time profile for its clinical application.

Abstract In this study, alpha nickel sulfide (α-NiS) nanosphere films have been successfully synthesized by electroplating the nickel nanosheet film on the indium tin oxide (ITO) glass substrate and sulfuring nickel-coated ITO glass substrate. First, we electrodeposited the nickel nanosheet films on the ITO glass substrates which were cut into a 0.5 × 1 cm2 size. Second, the nanosheet nickel films were annealed in vacuum-sealed glass ampoules with sulfur sheets at different annealing temperatures (300, 400, and 500 °C) for 4 h in vacuum-sealed glass ampoules. The α-NiS films were investigated by using X-ray diffraction (XRD), variable vacuum scanning electron microscopy (VVSEM), field emission scanning electron microscopy/energy dispersive spectrometer (FE-SEM/EDS), cyclic voltammogram (CV), electrochemical impedance spectroscopy (EIS), ultraviolet/visible/near-infrared (UV/Visible/NIR) spectra, and photoluminescence (PL) spectra. Many nanospheres were observed on the surface of the α-NiS films at the annealing temperature 400 °C for 4 h. We also used the high-resolution transmission electron microscopy (HR-TEM) for the analysis of the α-NiS nanospheres. We demonstrated that our α-NiS nanosphere film had a linear current response to different glucose concentrations. Additionally, our α-NiS nanosphere films were preserved at room temperature for five and a half years and were still useful for detecting glucose at low concentration.

Abstract Background Intermittent parathyroid hormone (PTH) can be used to treat osteoporosis of the spine and hip. However, whether it can be used to treat osteoporosis of the mandible is unclear. The purpose of this study was to explore the influence of applying intermittent PTH to ovariectomized rats on the trabecular bone microarchitecture of the mandible and femoral head. Methods Eighteen female rats were divided into three groups: the healthy group, ovariectomized (OVX) group, and OVX + PTH group. The OVX group and OVX + PTH group had an OVX at 8 weeks of age. The OVX + PTH group received intermittent PTH therapy for 12 weeks. The mandibles and femurs of all rats were removed at 20 weeks and were then scanned using microcomputed tomography (micro-CT). Results From the micro-CT analysis, the trabecular bone microarchitecture of the mandible and femoral head are offered as follows: (1) The bone volume fraction and trabecular thickness in the OVX group were lower than those in the healthy group. (2) The bone volume fraction and trabecular thickness in the OVX + PTH group approximated those in the healthy group. Conclusion The conclusions of this study regarding the trabecular bone microarchitecture of the mandible and femoral head are offered as follows: (1) The BV/TV and TbTh in the OVX group were lower than those in the healthy group. (2) The BV/TV and TbTh in the OVX + PTH group approximated those in the healthy group, therefore, intermittent PTH displayed high efficacy for treating femoral or mandibular deterioration of bone microstructure resulting from loss of ovarian function. Osteoporosis of the femur or mandible in the rats was ameliorated by intermittent PTH therapy.

Objective: To evaluate the effect of Shin-I essential oil inhalation on blood lactate changes in rats subjected to treadmill exercise. Methods: Adult male Sprague Dawley rats (n=12) were randomly divided into the control or the Shin-I group. Rats were subjected to a treadmill exercise program (15 m/min for 30 min). After exercise, rats were exposed to 200 μL of water or Shin-I essential oil, respectively, using a nebulizer for 180 min during the recovery period. Blood samples were collected every 15 min. Blood glucose and lactate concentrations were determined in a CMA 600 analyzer. Results: The basal glucose and lactate levels were no significantly different between two groups. After exercise, glucose levels were slightly increased to about 110%-120% of the basal level in both groups. Lactate levels of both groups reached to 110%-140% of basal levels during exercise. In the recovery period, lactate levels further increased to 180% of the basal level and were maintained at a plateau in the control group. However, lactate levels gradually decreased to 60%-65% of the basal level in the Shin-I group. Lactate clearance was significantly enhanced after Shin-I essential oil inhalation. Conclusions: Our results provide evidence that Shin-I essential oil inhalation may accelerate recovery after exercise in rats.

The literature shows that bone mineral density (BMD) and the geometric architecture of trabecular bone in the femur may be affected by inadequate dietary intake of Mg. In this study, we used microcomputed tomography (micro-CT) to characterize and quantify the impact of a low-Mg diet on femoral trabecular bones in mice.Four-week-old C57BL/6J male mice were randomly assigned to 2 groups and supplied either a normal or low-Mg diet for 8weeks. Samples of plasma and urine were collected for biochemical analysis, and femur tissues were removed for micro-CT imaging. In addition to considering standard parameters, we regarded trabecular bone as a cylindrical rod and used computational algorithms for a technical assessment of the morphological characteristics of the bones. BMD (mg-HA/cm3) was obtained using a standard phantom.We observed a decline in the total tissue volume, bone volume, percent bone volume, fractal dimension, number of trabecular segments, number of connecting nodes, bone mineral content (mg-HA), and BMD, as well as an increase in the structural model index and surface-area-to-volume ratio in low-Mg mice. Subsequently, we examined the distributions of the trabecular segment length and radius, and a series of specific local maximums were identified. The biochemical analysis revealed a 43% (96%) decrease in Mg and a 40% (71%) decrease in Ca in plasma (urine excretion).This technical assessment performed using micro-CT revealed a lower population of femoral trabecular bones and a decrease in BMD at the distal metaphysis in the low-Mg mice. Examining the distributions of the length and radius of trabecular segments showed that the average length and radius of the trabecular segments in low-Mg mice are similar to those in normal mice.

Transferring exogenous mitochondria has therapeutic effects on damaged heart, liver, and lung tissues. Whether this protective effect requires the symbiosis of exogenous mitochondria in host cells remains unknown. Here xenogenic mitochondria derived from a hamster cell line were applied to ischemic rat brains and rat primary cortical neurons. Isolated hamster mitochondria, either through local intracerebral or systemic intra-arterial injection, significantly restored the motor performance of brain-ischemic rats. The brain infarct area and neuronal cell death were both attenuated by the exogenous mitochondria. Although internalized mitochondria could be observed in neurons and astrocytes, the low efficacy of mitochondrial internalization could not completely account for the high rate of rescue of the treated neural cells. We further illustrated that disrupting electron transport or ATPase synthase in mitochondria significantly attenuated the protective effect, suggesting that intact respiratory activity is essential for the mitochondrial potency on neural protection. These results emphasize that nonsymbiotic extracellular mitochondria can provide an effective cell defense against acute injurious ischemic stress in the central nervous system.

PURPOSE:The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS) have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model. MATERIALS AND METHODS:Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups. RESULTS:NT-3 (Neurotrophin 3), BDNF (Brain derived neurotrophic factor), CNTF (Ciliary neurotrophic factor), and GDNF (Glia cell line derived neurotrophic factor) were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index) and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology. CONCLUSION:Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve regeneration in a long term nerve anastomosis model.

The aim of this study is to investigate the impact of serum Mg on bone mineral metabolism in chronic kidney disease (CKD) patients with or without diabetes. A total of 56 CKD patients not receiving dialysis were recruited and divided into two groups, one group of 27 CKD patients with diabetes and another group of 29 CKD patients without diabetes. Biochemical determinations were made, and the estimated glomerular filtration rate (eGFR) was measured. Bone mineral density was measured by dual-energy X-ray absorptiometry. Serum Mg was inversely correlated with serum Ca P=0.023 and positively correlated with serum parathyroid hormone (PTH) P=0.020, alkaline phosphatase P=0.044, and phosphate P=0.040 in the CKD patients with diabetes. The CKD patients with diabetes had lower serum albumin and a higher proportion of hypomagnesemia and osteoporosis than the nondiabetic patients did P

OBJECTIVE: The objective of this study was to evaluate the relationship between the trabecular bone microarchitecture and cortical bone morphology by using micro-computed tomography (micro-CT) and dental cone-beam computed tomography (dental CT). MATERIALS AND METHODS: Sixteen femurs and eight fifth lumbar vertebrae were collected from eight male Sprague Dawley rats. Four trabecular bone microarchitecture parameters related to the fifth lumbar vertebral body (percent bone volume [BV/TV], trabecular thickness [TbTh], trabecular separation [TbSp], and trabecular number [TbN]) were calculated using micro-CT. In addition, the volumetric cancellous bone grayscale value (vCanGrayscale) of the fifth lumbar vertebral body was measured using dental CT. Furthermore, four cortical bone morphology parameters of the femoral diaphysis (total cross-sectional area [TtAr], cortical area [CtAr], cortical bone area fraction [CtAr/TtAr], and cortical thickness [CtTh]) were calculated using both micro-CT and dental CT. Pearson analysis was conducted to calculate the correlation coefficients (r) of the micro-CT and dental CT measurements. Paired-sample t tests were used to compare the differences between the measurements of the four cortical bone morphology parameters obtained using micro-CT and dental CT. RESULTS: High correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV [r = 0.84] and TbTh [r = 0.84]) measured using micro-CT were observed. The absolute value of the four cortical bone morphology parameters may be different between the dental CT and micro-CT approaches. However, high correlations (r ranged from 0.71 to 0.90) among these four cortical bone morphology parameters measured using the two approaches were obtained. CONCLUSION: We observed high correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV and TbTh) measured using micro-CT, in addition to high correlations between the cortical bone morphology measured using micro-CT and dental CT. Further experiments are necessary to validate the use of dental CT on human bone.

Glucose mobilization and utilization in the periphery and central nervous system are important during exercise and are responsible for exercise efficacy. Magnesium (Mg) is involved in energy production and plays a role in exercise performance. This study aimed to explore the effects of Mg on the dynamic changes in glucose and lactate levels in the muscle, blood and brain of exercising rats using a combination of auto-blood sampling and microdialysis. Sprague-Dawley rats were pretreated with saline or magnesium sulfate (MgSO4, 90 mg/kg, i.p.) 30 min before treadmill exercise (20 m/min for 60 min). Our results indicated that the muscle, blood, and brain glucose levels immediately increased during exercise, and then gradually decreased to near basal levels in the recovery periods of both groups. These glucose levels were significantly enhanced to approximately two-fold (P

ObjectiveThis study compared the capabilities of dual-energy X-ray absorptiometry (DXA) and dental cone-beam computed tomography (CBCT) for predicting the cortical bone strength of rat femurs and tibias.Materials and methodsSpecimens of femurs and tibias obtained from 14 rats were first scanned with DXA to obtain the areal bone mineral density (BMD) of the midshaft cortical portion of the bones. The bones were then scanned using dental CBCT to measure the volumetric cortical bone mineral density (vCtBMD) and the cross-sectional moment of inertia (CSMI) for calculating the bone strength index (BSI). A three-point bending test was conducted to measure the fracture load of each femur and tibia. Bivariate linear Pearson analysis was used to calculate the correlation coefficients (r values) among the CBCT measurements, DXA measurements, and three-point bending parameters.ResultsThe correlation coefficients for the associations of the fracture load with areal BMD (measured using DXA), vCtBMD (measured using CBCT), CSMI (measured using CBCT), and BSI were 0.585 (p = 0.028) and 0.532 (p = 0.050) (for the femur and tibia, respectively), 0.638 (p = 0.014) and 0.762 (p = 0.002), 0.778 (p = 0.001) and 0.792 (pConclusionsCBCT was found to be superior to DXA for predicting cortical bone fracture loads in rat femurs and tibias. The BSI, which is a combined index of densitometric and geometric parameters, was especially useful. Further clinical studies are needed to validate the predictive value of BSI obtained from CBCT and should include testing on human cadaver specimens.

The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau 1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP + neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

The article presents the magnesium global network to promote research on magnesium in diseases focusing on covid-19. Topics discussed include this prompted establishment of a worldwide collaborative network with regular virtual meetings to brainstorm the associations between magnesium and COVID-19; and hypothesize that magnesium deficiency, a common but mostly unrecognized state in modern global societies, could be an important component of the susceptibility to SARS-CoV-2 infection.

Background We investigated the effects of dietary calcium (Ca) and magnesium (Mg) intakes on cardiovascular disease risks in older patients with diabetes. Methods In this cross-sectional study, 197 patients with type 2 diabetes aged 65 years and above were recruited. The 24-h dietary recalls and 1-week self-reported typical dietary intake patterns were collected. The Ca and Mg intakes of <67% of the recommended dietary allowance (RDA), 67%-100% of RDA, and >100% of RDA were defined as low, moderate, and high Ca and Mg intakes, respectively. Anthropometric measurements were determined and biochemical analysis of blood and urine was performed. Results Our data indicated that 60.9% and 87.3% of our patients were Ca and Mg intakes below RDA, respectively. Patients whose Ca intake was high or low (81.2%) had significantly higher C-reactive protein (CRP) than those whose Ca intake was moderate (p = 0.043). Furthermore, patients whose Mg intake was low (87.3%) had significantly higher CRP than that of those who took adequate Mg (p = 0.025). The dietary Ca:Mg intake ratios were highly correlated with CRP, platelet counts, and red blood cell distribution (p < 0.05). A dietary Ca:Mg intake ratio of 2.0-2.5 was significantly correlated to lower CRP levels (p = 0.013). Conclusions High or low calcium intake increases cardiovascular disease risks. We suggest that "moderate" intake of 402-600 mg Ca/day (approximately 67%-100% of Taiwan RDA for Ca) and adequate Mg intake (or meeting RDA for Mg) with Ca:Mg intake ratio of 2.0-2.5 are important for reducing cardiovascular disease risks in older patients with diabetes. [ABSTRACT FROM AUTHOR]

Background A new version of the CatWalk XT system was evaluated as a tool for detecting very subtle alteration in gait based on higher speed sample rate; the system could also demonstrate minor changes in neurological function. In this study, we evaluated the neurological outcome of sciatic nerve injury intervened by local injection of hyaluronic acid. Using the CatWalk XT system, we looked for differences between treated and untreated groups and differences within the same group as a function of time so as to assess the power of the Catwalk XT system for detecting subtle neurological change. Methods Peripheral nerve injury was induced in 36 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of two groups: Group I: crush injury as the control; Group II: crush injury and local application with hyaluronic acid. These animals were subjected to neurobehavior assessment, histomorphology evaluation, and electrophysiology study periodically. These data were retrieved for statistical analysis. Results The density of neurofilament and S-100 over the distal end of crushed nerve showed significant differences either in inter-group comparison at various time points or intra-group comparison from 7 to 28 days. Neuronal structure architecture, axon counts, intensity of myelination, electrophysiology, and collagen deposition demonstrate significant differences between the two groups. There was significant difference of SFI and angle of ankle in intergroup analysis from 7 to 28 days, but there were no significant differences in SFI and angle of ankle at time points of 7 and 14 days. In the Cat Walk XT analysis, the intensity, print area, stance duration, and swing duration all showed detectable differences at 7, 14, 21, and 28 days, whereas there were no significant difference at 7 and 14 days with CatWalk 7 testing. In addition, there were no significant differences of step sequence or regularity index between the two versions. Conclusion Hyaluronic acid augmented nerve regeneration as early as 7 days after crush injury. This subtle neurological alteration could be detected through the CatWalk XT gait analysis but not the SFI, angle of ankle, or CatWalk 7 methods. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus is a major global public health problem in the worldwide and is increasing in aging populations. Magnesium intake may be one of the most important factors for diabetes prevention and management. Low magnesium intake may exacerbate metabolic abnormalities. In this study, the relationships of magnesium intake with metabolic parameters, depression and physical activity in elderly patients with type 2 diabetes were investigated. Methods: This cross-sectional study involved 210 type 2 diabetes patients aged 65 years and above. Participants were interviewed to obtain information on lifestyle and 24-hour dietary recall. Assessment of depression was based on DSM-IV criteria. Clinical variables measured included anthropometric measurements, blood pressure, and biochemical determinations of blood and urine samples. Linear regression was applied to determine the relationships of magnesium intake with nutritional variables and metabolic parameters. Results: Among all patients, 88.6% had magnesium intake which was less than the dietary reference intake, and 37.1% had hypomagnesaemia. Metabolic syndromes and depression were associated with lower magnesium intake (p<0.05). A positive relationship was found between magnesium intake and HDL-cholesterol (p = 0.005). Magnesium intake was inversely correlated with triglyceride, waist circumference, body fat percent and body mass index (p<0.005). After controlling confounding factor, HDL-cholesterol was significantly higher with increasing quartile of magnesium intake (p for trend = 0005). Waist circumference, body fat percentage, and body mass index were significantly lower with increase quartile of magnesium intake (p for trend<0.001). The odds of depression, central obesity, high body fat percentage, and high body mass index were significantly lower with increasing quartile of magnesium intake (p for trend<0.05). In addition, magnesium intake was related to high physical activity level and demonstrated lower serum magnesium levels. Serum magnesium was not significantly associated with metabolic parameters. Conclusions: The majority of elderly type 2 diabetes who have low magnesium intake may compound this deficiency with metabolic abnormalities and depression. Future studies should determine the effects of increased magnesium intake or magnesium supplementation on metabolic control and depression in elderly people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background aims. Human mesenchymal stromal cells (hMSC) play a crucial role in tissue engineering and regenerative medicine, and have important clinical potential for cell therapy. However, many hMSC studies have been restricted by limited cell numbers and difficult detection in vivo. To expand the lifespan, hMSC are usually immortalized by virus-mediated gene transfer. However, these genetically modified cells easily lose critical phenotypes and stable genotypes because of insertional mutagenesis. Methods. We used a non-viral transfection method to establish human telomerase reverse transcriptase-immortalized cord blood hMSC (hTERT-cbMSC). We also established red fluorescent protein (RFP)-expressing hTERT-cbMSC (hTERT/RFP-cbMSC) by the same non-viral transfection method, and these cells were injected into a rat model with traumatic brain injury for in vivo detection analysis. Results. The hTERT-cbMSC could grow more than 200 population doublings with a stable doubling time and maintained differentiation capacities. hTERT/RFP-cbMSC could proliferate efficiently within 2 weeks at the injury location and could be detected easily under a fluorescent microscope. Importantly, both hTERT-cbMSC and hTERT/RFP-cbMSC showed no chromosomal abnormalities by karyotype analysis and no tumor formation in severe combined immunodeficient (SCID) mice by transplantation assay. Conclusions. We have developed immortalized cbMSC with hTERT expression and RFP expression, which will be useful tools for stem cell research and translational study. [ABSTRACT FROM AUTHOR]

The effect of magnesium supplementation on exercise performance remains controversial. In the present study, the effects of magnesium sulfate on exercise performance and blood glucose metabolism were examined. In order to provide a non-invasive measure of continuous exercise, we developed an auto-blood sampling system was coupled to a microdialysis analyzer to detect the dynamic changes in glucose metabolism in conscious and freely moving gerbils subjected to forced swimming. Gerbils were pretreated with saline or magnesium sulfate (90 mg kg−1, ip) 30 min before exercise. The duration times were significantly increased by 71% in the magnesium sulfate-treated groups ( p < 0.01) when compared with those in the control. Another group of gerbils were subjected to blood sampling assay. A catheter was implanted in the jugular vein of each gerbil for collecting blood samples by the computer-aided blood sampler. The basal levels of plasma glucose, lactate, and magnesium were 6,245 ± 662, 1,067 ± 309, and 590 ± 50 μM, respectively, with no significant difference between groups. Plasma glucose, lactate, and magnesium levels increased to 134 and 204%, 369 and 220%, and 155 and 422% of basal levels during swimming in both the control and magnesium sulfate-treated groups, respectively ( p < 0.05). Pretreatment with magnesium sulfate elevated glucose and magnesium levels to 175 and 302% of the basal levels ( p < 0.05), respectively, whereas pretreatment with magnesium sulfate reduced the lactate levels 150% of the basal level ( p < 0.05) during swimming. Furthermore, the magnesium levels increased to about 152–422% of basal levels during forced swimming and the recovery period ( p < 0.05). The present study demonstrates that magnesium sulfate improved the duration time of forced swimming exercise. In addition, magnesium raised glucose levels and attenuated lactate levels during forced swimming. These results indicate that positive effects of magnesium supplementation may contribute to the enhancement of exercise performance in athletes. [ABSTRACT FROM AUTHOR]

Although gait change is considered a useful indicator of severity in animal models of Parkinson's disease, systematic and extensive gait analysis in animal models of neurological deficits is not well established. The CatWalk-assisted automated gait analysis system provides a comprehensive way to assess a number of dynamic and static gait parameters simultaneously. In this study, we used the Catwalk system to investigate changes in gait parameters in adult rats with unilateral 6-OHDA-induced lesions and the rescue effect of dopaminergic neuron transplantation on gait function. Four weeks after 6-OHDA injection, the intensity and maximal area of contact were significantly decreased in the affected paws and the swing speed significantly decreased in all four paws. The relative distance between the hind paws also increased, suggesting that animals with unilateral 6-OHDA-induced lesions required all four paws to compensate for loss of balance function. At 8 weeks post-transplantation, engrafted dopaminergic neurons expressed tyrosine hydroxylase. In addition, the intensity, contact area, and swing speed of the four limbs increased and the distance between the hind paws decreased. Partial recovery of methamphetamine-induced rotational response was also noted. [ABSTRACT FROM AUTHOR]

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Abstract  Amniotic fluid mesenchymal stem cells (AFS) harbor the potential to improve peripheral nerve injury by inherited neurotrophic factor secretion, but present the drawback of the short-term survival after transplantation. Granulocyte-colony stimulating factor (G-CSF) has a diversity of functions, including anti-inflammatory and anti-apoptotic effects. This study was conducted to evaluate whether G-CSF could augment the neuroprotective effect of transplanted AFS against peripheral nerve injury. The potential involvement of anti-inflammation/anti-apoptosis effect was also investigated. Peripheral nerve injury was produced in Sprauge-Dawley rats by crushing left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. G-CSF (50 μg/kg) was administrated by intra-peritoneal injection for 7 consecutive days. Cell apoptosis, inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. Crush injury induced inflammatory response, disrupted nerve integrity, and impaired nerve function in sciatic nerve. Crush injury-provoked inflammation was attenuated in groups receiving G-CSF but not in AFS only group. In transplanted AFS, marked apoptosis was detected and this event was reduced by G-CSF treatment. Increased nerve myelination and improved motor function were observed in AFS transplanted, G-CSF administrated, and AFS/G-CSF combined treatment groups. Significantly, the combined treatment showed the most beneficial effect. In conclusion, the concomitant treatment of AFS with G-CSF augments peripheral nerve regeneration which may involve the suppression of apoptotic death in implanted AFS and the attenuation of inflammatory response. [ABSTRACT FROM AUTHOR]

Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits. [ABSTRACT FROM AUTHOR]

Aim: To examine if magnesium lithospermate B (MLB) extracted from Danshen, the dried roots of Salvia miltiorrhiza, may act as an active component responsible for the cardiac therapeutic effect of this traditional Chinese herb via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Moreover, we wanted to test if MLB may provide neuroprotection against ischemic stroke as observed for cardiac glycosides. Methods: Similarity in the chemical structure and molecular configuration between MLB and ouabain was analyzed. The inhibition potency of MLB and ouabain on Na+,K+-ATPase activity of a commercial product, as well as in purified membrane fractions from rat brain and heart tissues, was examined and compared. Neuroprotective effect of MLB against ischemic stroke was also evaluated using a cortical brain slice-based assay model. Results: Dose-dependent inhibition on the commercial Na+,K+- ATPase equivalent to that for ouabain was observed for MLB of approximately half dosage by weight. This relative potency of ouabain and MLB was also observed for their inhibition on Na+,K+-ATPase activity of plasma membrane purified from rat tissues, although these 2 inhibitors exhibited somewhat lower competence in these crude extracts. In ischemic gerbil brains, post-treatment with MLB significantly reduced the infarct size, visualized by 2,3,5-triphenyltetrazolium chloride staining, by approximately 55% when compared with the control group. Conclusion: These results evidently suggest that the cardiac therapeutic effect of Danshen should be at least partly attributed to the effective inhibition of Na+,K+- ATPase by MLB, and that MLB provides anti-ischemic neuroprotection in gerbils subjected to focal ischemia and reperfusion. [ABSTRACT FROM AUTHOR]

This investigation examined the acute effects of magnesium on the dynamic changes of brain glucose, lactate, pyruvate and magnesium levels in conscious gerbils during forced swimming. Gerbils were pretreated with saline (control group) and magnesium sulfate (90 mg kg−1, intraperitoneal injection) before a 15 min forced swimming period. The basal levels of glucose, pyruvate, lactate, and magnesium in brain dialysates were 338 ± 18, 21 ± 2, 450 ± 39, and 2.1 ± 0.1 μM, respectively, with no significant difference between groups. Magnesium levels were found slightly higher (but not significant) in the magnesium-treated group. However, brain glucose and pyruvate levels in the control group decreased to about 50 and 60% of the basal level ( P = 0.01) after swimming, respectively. Pretreatment with magnesium sulfate immediately increased glucose levels to about 140% of the basal level, and increased pyruvate levels to about 150% of the basal level during forced swimming ( P = 0.01). Both glucose and pyruvate levels returned to the basal level after 30 min of the recovery. The lactate levels of the control group increased to about 160% of the basal level ( P = 0.01) during swimming, whereas pretreatment with magnesium sulfate attenuated lactate levels to 130% of the basal level ( P = 0.01). Magnesium supplementation may be beneficial because it provides an additional glucose source and may also promote the recovery of energy substrates in the brain during and after forced exercise. In order to achieve optimal physical performance, further investigation as to dosage of magnesium supplementation is needed. [ABSTRACT FROM AUTHOR]

Ginkgo biloba exerts many pharmacological actions. It possesses antioxidant properties, the ability of neurotransmitter/receptor modulation and antiplatelet activation factor. This research is designed to investigate the neuroprotective effects of long-term treatment with EGb761 (a standard form of the extract of Ginkgo biloba leaf) in combination with MgSO4, FK506, or MK-801 on the infarct volume of male gerbils' brain induced by unilateral middle cerebral artery occlusion (MCAO). Thirty-five gerbils fed a standard diet were intragastrically given water or EGb761 (100 mg/kg/day) for one week. Five randomized groups were established: control (n = 7), EGb761 (n = 8), EGb761 + MgSO4 (n = 7), EGb761 + FK506 (n = 7), and EGb761 + MK-801 (n = 6). The three drug-combination groups were injected with MgSO4 (90 mg/kg), FK506 (0.5 mg/kg), or MK-801 (1 mg/kg), respectively 30 min before MCAO. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation for 24 hours. Postmortem infarct volumes were determined by quantitative image analysis of 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections. Results showed that the total infarct volumes of the four treated groups either EGb761 alone or in combination with drugs were lower than the control group by 36.1% (EGb761 alone), 40.3% (EGb761 + MgSO4), 35.3% (EGb761 + FK506), and 56.4% (EGb761 + MK-801), respectively (p < 0.01). The main affected areas of the brain in the four treated groups were significantly focused between 4 and 6 mm from the frontal pole, when compared to the control group (p < 0.01). All animals in the five groups had infarctions in both cortex and subcortex. These results indicate that long-term pre-treatment of EGb761 administered either alone or in combination with drugs significantly effective neuroprotection on infarct volume in gerbil ischemic brains. [ABSTRACT FROM AUTHOR]

Cell death after cerebral ischemia is mediated by the accumulation of excitatory amino acids, calcium influx into cells and the generation of free radicals. The aim of this study was to evaluate changes in energy-related metabolites in the striatum of gerbils subjected to focal cerebral ischemia after pretreatment with Ginkgo biloba extract (EGb761), a well-known antioxidant, and FK506, a calcium-dependent phosphatase calcineurin inhibitor. Ischemia was induced by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min. A microdialysis probe was inserted into the right striatum to monitor extracellular glucose, lactate and pyruvate levels. This study showed decreases in glucose (10% of the baseline), pyruvate (20% of the baseline) and lactate (60% of the baseline), and a 5-fold increase in the lactate to pyruvate ratio during ischemia in the control group. Both EGb761 treatment and the combination (EGb761 and FK506) therapy significantly preserved glucose (50% of the baseline) and pyruvate (60% of the baseline) levels during ischemia. The marked increase in the lactate to pyruvate ratio was not observed in the combination group. These results suggest that preservation of cellular energy metabolism during cerebral ischemia and after restoration with reperfusion may contribute to the neuroprotective effects of EGb761 and FK506. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The present study examined effects of the combined administration of naloxone (NX) and indomethacin (IM) on nigrostriatal catecholamines and locomotor activity after intranigral lipopolysaccharide (LPS) injection in Sprague-Dawley rats. NX plus IM was given 3 days after LPS injection; it significantly (P < .05) reversed LPS inflammation on nigrostriatal dopamine (DA) and nigral serotonin (5-HT) and nigral homovanillic acid (HVA)/DA ratio and nigrostriatal 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio. It also tended to ameliorate the locomotor hyperactivity. However, NX plus IM given 30 min before LPS could not satisfactorily protect against LPS's damage both biochemically and behaviorally. These results reveal that NX plus IM may protect against LPS on DA, 5-HT, and motor function after LPS injection but not before. Thus it suggests that the combined treatment of NX and IM gives a potent therapy, but not prevention, of LPS-induced inflammation and also protect nigrostriatal dopaminergic and serotoninergic systems against LPS in rats. [ABSTRACT FROM AUTHOR]

In this investigation, microdialysis has been used to study the effects of 1-methyl-4-phenylpyridinium (MPP[sup +]), an inhibitor of mitochondrial complex I and α-ketoglutarate dehydrogenase and the active metabolite of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP), on extracellular concentrations of glutathione (GSH) and cysteine (CySH) in the rat striatum and substantia nigra (SN). During perfusion of a neurotoxic concentration of MPP[sup +] (2.5 mM) into the rat striatum or SN, extracellular concentrations of GSH and CySH remain at basal levels (both ∼2 µM). However, when the perfusion is discontinued, a massive but transient release of GSH occurs, peaking at 5,000% of basal levels in the striatum and 2,000% of basal levels in the SN. The release of GSH is followed by a slightly delayed and smaller elevation of extracellular concentrations of CySH that can be blocked by the γ-glutamyl transpeptidase (γ-GT) inhibitor acivicin. Low-molecular-weight iron and extracellular hydroxyl radical (OH...) have been implicated as participants in the mechanism underlying the dopaminergic neurotoxicity of MPTP/MPP[sup +]. During perfusion of Fe[sup 2+] (OH...) into the rat striatum and SN, extracellular levels of GSH also remain at basal levels. When perfusions of Fe[sup 2+] are discontinued, a massive transient release of GSH occurs followed by a delayed, small, but progressive elevation of extracellular CySH level that again can be blocked by acivicin. Previous investigators have noted that extracellular concentrations of the excitatory/excitotoxic amino acid glutamate increase dramatically when perfusions of neurotoxic concentrations of MPP[sup +] are discontinued. This observation and the fact that MPTP/MPP[sup +] causes the loss of nigrostriatal GSH without corresponding increases of glutathione disulfide (GSSG) and the results of the present investigation suggest that the release and &gamma... [ABSTRACT FROM AUTHOR]

Serum magnesium (Mg) levels are closely controlled through a variety of Mg transporters and ionic channels during physiological conditions. These levels have been shown to increase during exercise. However, the effect of Mg transporter expression during exercise remains to be determined. The purpose of this study was to examine the gene expression of SLC41A1, a Na+/Mg2+ exchanger, during exercise. In the present study, male C57BL/6JNarl mice (n = 16, 8 weeks old) were subjected to 3 h forced exercise on a treadmill. The mice in the control and Mg groups were injected with saline and Mg (MgSO4, 90 mg/kg, intraperitoneal), respectively. Blood samples were obtained at three time points: prior to, following and 24 h after exercise. The gene expression levels of SLC41A1 were significantly downregulated to 23.6 ± 4.6 and 12.6 ± 10.2% following exercise in the control and Mg groups, respectively. The expression levels returned to the basal levels 24 h after exercise in the two groups and there was no significant difference found between the two groups. The downregulated role of SLC41A1 expression and its interaction with the Mg status in exercise requires further investigation. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the leading cause of death and permanent disabled, affecting the young and adults in the most productive years of their lives. Recently, human amniotic fluid mesenchymal stem cells (hAFMSC) were reported to ameliorate functional deficits after sciatic nerve injury in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. Adenovirus-glial derived neurotrophic factor (Ad-GDNF) can preserve neuronal fibers and promote locomotor recovery on rats subjected to spinal cord contusion. Thus, we transfected hAFMSCs with the Ad-GDNF and investigated whether these cells contributed to improved functional recovery in TBI rats. The hAFMSCs were plate in 5 ml of -MEM supplemented with 20% FBS in a T75-flask and incubated at 37 °C with 5% humidified CO[sub2]. The Ad-GDNF and Ad-green fluorescent protein (Ad-GFP) were prepared. The hAFMSCs were infected with Ad-GFP and Ad-GDNF. A Dragonfly fluid percussion device was used to induce a lateral fluid percussion injury model of moderate TBI in adult SD rats. The GDNF gene-modified hAFMSCs (1 x 106) were injected into the right dorsolateral striatum 4 mm and lateral 3 mm to bregma over a 2.5-min period. Motor function recovery experiment was assayed using a rotarod test. Our preliminary findings are (1) the Ad-GFP transfected hAFMSCs after 3 days expressed the florescence in vitro, (2) 7 days after transplantation, the GFP and CM-Dil positive cells exhibited in the subventricle zone-ofactory bulb neural regeneration tract, the MSC-GDNF treatment group showed better motor behavioral recovery from 3 days through 14 days than control group, and (4) the improved effect can prolong to 28 days after transplantation. These preliminary data suggest that hAFMSCs transfected with the GDNF gene may be useful in the treatment of brain trauma and may represent a new strategy for the treatment of TBI. [ABSTRACT FROM AUTHOR]

Natto is a traditional Japanese food prepared from fermented soybeans. nattokinase (NK) is considered one of the most active functional ingredients in natto. The present study evaluated the neuroprotective effects of NK in gerbils subjected to focal cerebral ischemia. The gerbils were separated into four groups: control group, ischemic group and two NK groups (4 and 40 mg/day i.g. for 7 days). All gerbils were fed standard chow with or without NK prior to cerebral ischemia. Focal cerebral ischemia was induced by the occlusion of the right common carotid artery and middle cerebral artery for 60 min, followed by reperfusion. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. Anti-thrombotic effects of NK, such as fibrinogen, prothrombin time and activated partial thromboplastin time, were also determined. Our data showed that NK significantly reduced infarct volumes by 54-68% (p < 0.01), compared to the ischemic group. Prothrombin time was not significantly different in all groups. However, low dosage NK (4 mg/day) reversed ischemic-induced increase in fibrinogen concentrations and activated partial thromboplastin time. In summary, the data indicated that oral intake of NK for 7 days may alter fibrinolytic activity and provide neuroprotective effects against focal cerebral ischemia in gerbils. [ABSTRACT FROM AUTHOR]