Acute and Prolonged Effects of 300 sec of Static, Dynamic, and Combined Stretching on Flexibility and Muscle Force.

Static stretching (SS), dynamic stretching (DS), and combined stretching (CS; i.e., DS+SS) are commonly performed as warm-up exercises. However, the stretching method with the greatest effect on flexibility and performance remains unclear. This randomized crossover trial examined acute and prolonged effects of SS, DS, and CS on range of motion (ROM), peak passive torque (PPT), passive stiffness, and isometric and concentric muscle forces. Twenty healthy young men performed 300 sec of active SS, DS, or CS (150-sec SS followed by 150-sec DS and 150-sec DS followed by 150-sec SS) of the right knee flexors on four separate days, in random order. Subsequently, we measured ROM, PPT, and passive stiffness during passive knee extension. We also measured maximum voluntary isometric and concentric knee flexion forces and surface electromyographic activities during force measurements immediately before, immediately after, and 20 and 60 min after stretching. All stretching methods significantly increased ROM and PPT, while significantly decreasing isometric knee flexion force (all p < 0.05). These changes lasted 60 min after all stretching methods; the increases in ROM and PPT and the decreases in isometric muscle force were similar. All stretching methods also significantly decreased passive stiffness immediately after stretching (all p < 0.05). Decreases in passive stiffness tended to be longer after CS than after SS or DS. Concentric muscle force was decreased after SS and CS (all p < 0.05). On the other hand, concentric muscle force was unchanged after DS, while the decreases in surface electromyographic activities during concentric force measurements after all stretching methods were similar. Our results suggest that 300 sec of SS, DS, and CS have different acute and prolonged effects on flexibility and muscle force.

Effects of High-Intensity Stretch with Moderate Pain and Maximal Intensity Stretch without Pain on Flexibility.

In this study, we aimed to identify the time course effects of different intensities of static stretch (SST) (maximal intensity without pain vs. high-intensity with moderate pain) on flexibility. This study included 16 healthy students (8 men and 8 women) who performed 1) 5-minute SST at 100%, 2) 110%, and 3) 120% intensity, as well as 4) no stretching (control) in a random sequence on four separate days. Static passive torque (SPT), hamstring electromyography (EMG), and pain intensity were continuously recorded during SST. We assessed markers of stiffness, range of motion (ROM), and maximal dynamic passive torque (DPTmax) before SST and 0, 15, 30, 45, 60, 75, and 90 minutes after SST. Stiffness decreased and ROM and DPTmax increased significantly immediately after SST at the three different intensity levels (p < 0.05). The effects of SST at 120% intensity were stronger and lasted longer than the effects of SST at 110% and 100% intensity (stiffness: -17%, -9%, and -7%, respectively; ROM: 14%, 10%, and 6%, respectively; DPTmax: 15%, 15%, and 9%, respectively). SPT decreased after SST at all intensities (p < 0.05). SST at 120% intensity caused a significantly greater reduction in SPT than SST at 100% intensity (p < 0.05). Pain intensity and EMG activity increased immediately after the onset of SST at 120% intensity (p < 0.05), although these responses were attenuated over time. Stretching intensity significantly correlated with the degree of change in ROM and stiffness (p < 0.05). These results support our hypothesis that stretch-induced flexibility is amplified and prolonged with an increase in stretch intensity beyond the pain threshold. Additional studies with more participants and different demographics are necessary to examine the generalizability of these findings.

Acute and chronic effects of static stretching at 100% versus 120% intensity on flexibility.

PURPOSE: The acute effects of static stretching have been frequently studied, but the chronic effects have not been studied concurrently. Thus, this study aimed to investigate both the acute and chronic effects of static stretching at different intensities on flexibility. METHODS: Twenty-three healthy men were randomly assigned to perform 1 min of static stretching 3 days/week for 4 weeks at 100% intensity (n = 12) or 120% intensity (n = 11). The acute effects of stretching were assessed by measuring the range of motion (ROM), peak passive torque, and passive stiffness before and after every stretching session; the chronic effects of stretching were assessed by measuring these outcomes at baseline and after 2 and 4 weeks of stretching. RESULTS: Compared with the 100% intensity group, the 120% intensity group had significantly greater acute increases in ROM after all 12 sessions, a significantly greater decrease in passive stiffness after 11 of 12 sessions, and a significantly greater increase in peak passive torque after six of 12 sessions. Regarding the chronic effects, ROM was significantly increased in both groups after 2 and 4 weeks of stretching. Peak passive torque significantly increased in the 100% intensity group after 2 and 4 weeks of stretching, and after 4 weeks in the 120% intensity group. CONCLUSION: Stretching at 120% intensity resulted in significantly greater acute improvements in ROM, peak passive torque, and stiffness than stretching at 100% intensity. Four weeks of stretching increased ROM and peak passive torque but did not decrease passive stiffness, regardless of the stretching intensity.

p62/SQSTM1 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in oxidative muscle.

Increased muscle contractile activity, as observed with regular exercise, prevents oxidative stress-induced muscle wasting, at least partially, by improving the antioxidant defense system. Phosphorylated p62/sequestosome1 competitively binds to the Kelch-like ECH-associated protein 1, activating nuclear factor erythroid 2-related factor 2 (Nrf2), which stimulates transcription of antioxidant/electrophile responsive elements. However, it remains to be determined if this process is activated by regular exercise in skeletal muscle. Here, we demonstrate that muscle contractile activity increases antioxidants, Nrf2 translocation into nuclei, and Nrf2 DNA-binding activity in association with increased p62 phosphorylation (Ser351) in mouse oxidative skeletal muscle. Skeletal muscle-specific loss of Nrf2 [i.e., Nrf2 muscle-specific knockout (mKO) mice] abolished the expression of the Nrf2 target antioxidant gene NAD(P)H-quinone oxidoreductase 1 (NQO1) in both glycolytic and oxidative muscles but reduced exercise-mediated increases of antioxidants (i.e., copper/zinc superoxide dismutase (SOD) and extracellular SOD only in oxidative muscle. Interestingly, skeletal muscle-specific loss of p62 (i.e., p62 mKO mice) also abolished the expression of NQO1 and reduced exercise-mediated increases of the same antioxidants in soleus muscle. Collectively, these findings indicate that p62 and Nrf2 cooperatively regulate the exercise-mediated increase of antioxidants in oxidative muscle.-Yamada, M., Iwata, M., Warabi, E., Oishi, H., Lira, V. A., Okutsu, M. p62/SQSTM1 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in oxidative muscle.

Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but not exercise training-induced angiogenesis.

Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.

Hamstring Stiffness Returns More Rapidly After Static Stretching Than Range of Motion, Stretch Tolerance, and Isometric Peak Torque.

Context: Hamstring injuries are common, and lack of hamstring flexibility may predispose to injury. Static stretching not only increases range of motion (ROM) but also results in reduced muscle strength after stretching. The effects of stretching on the hamstring muscles and the duration of these effects remain unclear. Objective: To determine the effects of static stretching on the hamstrings and the duration of these effects. Design: Randomized crossover study. Setting: University laboratory. Participants: A total of 24 healthy volunteers. Interventions: The torque-angle relationship (ROM, passive torque [PT] at the onset of pain, and passive stiffness) and isometric muscle force using an isokinetic dynamometer were measured. After a 60-minute rest, the ROM of the dynamometer was set at the maximum tolerable intensity; this position was maintained for 300 seconds, while static PT was measured continuously. The torque-angle relationship and isometric muscle force after rest periods of 10, 20, and 30 minutes were remeasured. Main Outcome Measures: Change in static PT during stretching and changes in ROM, PT at the onset of pain, passive stiffness, and isometric muscle force before stretching were compared with 10, 20, and 30 minutes after stretching. Results: Static PT decreased significantly during stretching. Passive stiffness decreased significantly 10 and 20 minutes after stretching, but there was no significant prestretching versus poststretching difference after 30 minutes. PT at the onset of pain and ROM increased significantly after stretching at all rest intervals, while isometric muscle force decreased significantly after all rest intervals. Conclusions: The effect of static stretching on passive stiffness of the hamstrings was not maintained as long as the changes in ROM, stretch tolerance, and isometric muscle force. Therefore, frequent stretching is necessary to improve the viscoelasticity of the muscle-tendon unit. Muscle force decreased for 30 minutes after stretching; this should be considered prior to activities requiring maximal muscle strength.

Dynamic Stretching Has Sustained Effects on Range of Motion and Passive Stiffness of the Hamstring Muscles.

Dynamic stretching (DS) is often performed during warm-up to help avoid hamstring muscle injuries, increase joint flexibility, and optimize performance. We examined the effects of DS of the hamstring muscles on passive knee extension range of motion (ROM), passive torque (PT) at the onset of pain (as a measure of stretch tolerance), and passive stiffness of the muscle-tendon unit over an extended period after stretching. Twenty-four healthy subjects participated, with 12 each in the experimental and control groups. Stretching was performed, and measurements were recorded using an isokinetic dynamometer pre-intervention, and at 0, 15, 30, 45, 60, 75, and 90 min post-intervention. DS consisted of ten 30-s sets of 15 repetitions of extension and relaxation of the hamstrings. ROM increased significantly (range, 7%-10%) immediately after DS, and the increase was sustained over 90 min. PT at the onset of pain also increased immediately by 10% but returned to baseline by 30 min. Passive stiffness decreased significantly (range, 7.9%-16.7%) immediately after DS, and the decrease was sustained over 90 min. Post-DS values were normalized to pre-DS values for the respective outcomes in both groups. ROM was significantly higher (range, 7.4%-10%) and passive stiffness was significantly lower (range, 5.4%-14.9%) in the experimental group relative to the control group at all time points. Normalized PT values at the onset of pain were significantly higher in the experimental group at 0-15 min than in the controls, but the differences were smaller at 30-45 min and not significant thereafter. We conclude that DS increases ROM and decreases passive stiffness in a sustained manner, and increases PT at the onset of pain for a shorter period. Overall, our results indicate that when performed prior to exercise, DS is beneficial for the hamstring muscles in terms of increasing flexibility and reducing stiffness.

Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro.

It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid-induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid-induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation. The synthetic glucocorticoid dexamethasone decreased myotube diameter and protein content, and heat stress prevented the morphological and biochemical glucocorticoid effects. Heat stress also attenuated increases in mRNAs of regulated in development and DNA damage responses 1 (REDD1) and Kruppel-like factor 15 (KLF15). Heat stress recovered the dexamethasone-induced inhibition of PI3K/Akt signaling. These data suggest that changes in anabolic and catabolic signals are involved in heat stress-induced protection against glucocorticoid-induced muscle atrophy. These results have a potentially broad clinical impact because elevated glucocorticoid levels are implicated in a wide range of diseases associated with muscle wasting. J. Cell. Physiol. 232: 650-664, 2017. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.

Acute Effects of the Different Intensity of Static Stretching on Flexibility and Isometric Muscle Force.

Kataura, S, Suzuki, S, Matsuo, S, Hatano, G, Iwata, M, Yokoi, K, Tsuchida, W, Banno, Y, and Asai, Y. Acute effects of the different intensity of static stretching on flexibility and isometric muscle force. J Strength Cond Res 31(12): 3403-3410, 2017-In various fields, static stretching is commonly performed to improve flexibility, whereas the acute effects of different stretch intensities are unclear. Therefore, we investigated the acute effects of different stretch intensities on flexibility and muscle force. Eighteen healthy participants (9 men and 9 women) performed 180-second static stretches of the right hamstrings at 80, 100, and 120% of maximum tolerable intensity without stretching pain, in random order. The following outcomes were assessed as markers of lower limb function and flexibility: static passive torque (SPT), range of motion (ROM), passive joint (muscle-tendon) stiffness, passive torque (PT) at onset of pain, and isometric muscle force. Static passive torque was significantly decreased after all stretching intensities (p ≤ 0.05). Compared with before stretching at 100 and 120% intensities, ROM and PT were significantly increased after stretching (p ≤ 0.05), and passive stiffness (p = 0.05) and isometric muscle force (p ≤ 0.05) were significantly decreased. In addition, ROM was significantly greater after stretching at 100 and 120% than at 80%, and passive stiffness was significantly lower after 120% than after 80% (p ≤ 0.05). However, all measurements except SPT were unchanged after 80% intensity. There was a weak positive correlation between the intensities of stretching and the relative change for SPT (p ≤ 0.05), a moderate positive correlation with ROM (p ≤ 0.05), and a moderate positive correlation with passive stiffness (p ≤ 0.05). These results indicate that static stretching at greater intensity is more effective for increasing ROM and decreasing passive muscle-tendon stiffness.

Changes in force and stiffness after static stretching of eccentrically-damaged hamstrings.

PURPOSE: This study compared responses to static stretching between eccentrically damaged and non-damaged muscles. METHODS: Twelve young men performed 60 maximum knee flexor eccentric contractions of one leg, and received a 300-s continuous passive static stretching at tolerable intensity without pain to both knee flexors at 2 and 4 days after the eccentric exercise. Range of motion (ROM) and passive stiffness during knee extension, passive torque at onset of pain (PT), maximum voluntary isometric (MVC-ISO) and isokinetic concentric contraction torque (MVC-CON), and visual analogue scale (VAS) for muscle soreness were measured before, immediately after, 60 min, 2 and 4 days after exercise as well as before, immediately after, 20 and 60 min after the stretching. Changes in these variables after eccentric exercise and stretching were compared between limbs. RESULTS: The eccentric exercise decreased MVC-ISO, MVC-CON, ROM and PT, and increased passive stiffness and VAS (p < 0.05), suggesting that muscle damage was induced to the knee flexors. ROM and PT increased after stretching for both limbs; however, the magnitude of the increase was greater (p < 0.05) for the damaged than non-damaged limb. Passive stiffness decreased for both limbs similarly (4-7 %) at immediately after stretching (p < 0.05). Significant decreases in MVC-ISO torque (7-11 %) after stretching were observed only for the non-damaged limb (p < 0.05), but MVC-CON torque did not change after stretching for both limbs. VAS decreased for the exercised limb after stretching (p < 0.05). CONCLUSIONS: These results suggest that the static stretching at tolerable intensity without pain produced greater positive effects on damaged than non-damaged muscles.

Acute effects of different stretching durations on passive torque, mobility, and isometric muscle force.

Static stretching is widely applied in various disciplines. However, the acute effects of different durations of stretching are unclear. Therefore, this study was designed to investigate the acute effects of different stretching durations on muscle function and flexibility, and provide an insight into the optimal duration of static stretching. This randomized crossover trial included 24 healthy students (17 men and 7 women) who stretched their right hamstrings for durations of 20, 60, 180, and 300 seconds in a random order. The following outcomes were assessed using an isokinetic dynamometer as markers of lower-limb function and flexibility: static passive torque (SPT), dynamic passive torque (DPT), stiffness, straight leg raise (SLR), and isometric muscle force. Static passive torque was significantly decreased after all stretching durations (p < 0.05). Static passive torque was significantly lower after 60, 180, and 300 seconds of stretching compared with that after 20-second stretching, and stiffness decreased significantly after 180- and 300-second stretching (p < 0.05). In addition, DPT and stiffness were significantly lower after 300 seconds than after 20-second stretching (p < 0.05), and SLR increased significantly after all stretching durations (p < 0.05). Straight leg raise was higher after 180- and 300-second stretching than after 20-second stretching and higher after 300-second stretching than after 60-second stretching (p < 0.05). Isometric muscle force significantly decreased after all stretching durations (p < 0.05). Therefore, increased duration of stretching is associated with a decrease in SPT but an increase in SLR. Over 180 seconds of stretching was required to decrease DPT and stiffness, but isometric muscle force decreased regardless of the stretching duration. In conclusion, these results indicate that longer durations of stretching are needed to provide better flexibility.

Therapeutic potential of ASP3258, a selective phosphodiesterase 4 inhibitor, on chronic eosinophilic airway inflammation.

We investigated and compared the pharmacological effects of a PDE4 inhibitor ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), with those of roflumilast, the most clinically advanced PDE4 inhibitor known. ASP3258 inhibited human PDE4A, 4B, 4C, and 4D with respective IC(50) values of 0.036, 0.050, 0.45, and 0.035 nmol/l, all approximately 3-6 times more potent than roflumilast. ASP3258 inhibited LPS-induced TNF-α production and PHA-induced IL-5 production in human whole blood cells with respective IC(50) values of 110 and 100 nmol/l, both approximately 10 times less potent than roflumilast. Repeatedly administered ASP3258 and roflumilast both suppressed chronic airway eosinophilia induced by repeated exposure to ovalbumin in Brown Norway rats with respective ED(50) values of 0.092 and 0.17 mg/kg. We also evaluated the toxicological profiles of ASP3258. Although PDE4 inhibitors induce emesis by mimicking the pharmacological action of an α(2)-adrenoceptor antagonist, repeated administration of ASP3258 (3 mg/kg) had no such inhibitory effect on rats anesthetized with α(2) - adrenoceptor agonist. PDE4 inhibitors are also known to induce vascular injury in rats. Although repeatedly administered ASP3258 (3 and 10 mg/kg) significantly increased plasma fibrinogen, a biomarker for toxicity, 1 mg/kg of ASP3258 did not. These results suggest that ASP3258 is an attractive PDE4 inhibitor for treating chronic eosinophilic airway inflammation due to asthma.

Involvement of nitric oxide in a rat model of carrageenin-induced pleurisy.

Some evidence indicates that nitric oxide (NO) contributes to inflammation, while other evidence supports the opposite conclusion. To clarify the role of NO in inflammation, we studied carrageenin-induced pleurisy in rats treated with an NO donor (NOC-18), a substrate for NO formation (L-arginine), and/or an NO synthase inhibitor (S-(2-aminoethyl) isothiourea or N(G)-nitro-L-arginine). We assessed inflammatory cell migration, nitrite/nitrate values, lipid peroxidation and pro-inflammatory mediators. NOC-18 and L-arginine reduced the migration of inflammatory cells and edema, lowered oxidative stress, and normalized antioxidant enzyme activities. NO synthase inhibitors increased the exudate formation and inflammatory cell number, contributed to oxidative stress, induced an oxidant/antioxidant imbalance by maintaining high O(2) (-), and enhanced the production of pro-inflammatory mediators. L-arginine and NOC-18 reversed the proinflammatory effects of NO synthase inhibitors, perhaps by reducing the expression of adhesion molecules on endothelial cells. Thus, our results indicate that NO is involved in blunting-not enhancing-the inflammatory response.

The protective role of localized nitric oxide production during inflammation may be mediated by the heme oxygenase-1/carbon monoxide pathway.

Nitric oxide (NO) is an important part of the host defense mechanism; however, it displays both pro- and anti-inflammatory properties depending on its location and concentration. Importantly, excessive or inappropriate NO production can cause tissue damage. Systemic and local administration of NO synthase (NOS) inhibitors ameliorates and may exacerbate the inflammatory response, respectively. Here, we used a carrageenan-induced pleurisy model of acute inflammation in rats to confirm the location-dependent effects of NO and investigate the underlying mechanisms. As expected, localized suppression of NO production exacerbated inflammation, as evidenced by increased pleural exudate volumes and leukocyte counts and enhanced activity of enzymes related to oxidative stress. In contrast, local NO supplementation reduced leukocyte infiltration, vascular permeability, and the activity of oxidative stress-related enzymes. Interestingly, inhibition of heme oxygenase-1 (HO-1) reversed the anti-inflammatory effects of localized NO production, while the addition of hemin (HO-1 substrate) or carbon monoxide (CO; HO-1 metabolite) decreased leukocyte migration and exudation. Together, these findings confirm a protective role for NO at the inflammatory site, which appears to be mediated via NOS induction of the HO-1/CO pathway. Thus, NO supplementation may be a potential new treatment for oxidative stress-associated inflammatory diseases.

Median nerve injury does not contribute to early onset of decreased grip strength due to repetitive reaching and grasping tasks in rats.

BACKGROUND: Workplace risk factors, such as repetitive tasks, can cause work-related musculoskeletal disorders. In a rat model, decreased grip strength and median nerve injury develop following repetitive reaching and grasping tasks, involving negligible force. OBJECTIVE: We investigated whether median nerve injury is involved in the early onset of decreased grip strength due to such tasks METHODS: Sprague-Dawley rats were divided into: non-task-performing (0-week) and task-performing (1-, 2-, and 3-week) groups. After an initial training period, the task-performing groups continued to perform the task for 2 h/day, 3 days/week, for 1-3 weeks. Grip strength and relative muscle weight of the flexor digitorum superficialis (FDS) muscle were measured. Median nerve injury was evaluated by histopathology and immunohistochemistry. RESULTS: Grip strength of the reach limb (forelimb used in tasks) was significantly lower in the 3-week group compared with the other groups and was significantly lower than that of the non-reach limb in all groups. There were no significant differences in the relative FDS muscle weights of either limb among groups. No evidence of median nerve demyelination was observed and no cells expressed activating transcription factor-3, a specific marker of peripheral nerve injury, in the anterior horn of the spinal cord. CONCLUSION: Median nerve injury does not contribute to the decreased grip strength caused by 3 weeks of repetitive reaching and grasping tasks, involving negligible force, in rats.

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells.

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.

The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells.

Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 microM) suppressed OGD- and H(2)O(2)-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 microM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.

Effects of passive stretching on muscle injury and HSP expression during recovery after immobilization in rats.

OBJECTIVE: Stretching exercise is known to induce muscle hypertrophy and is implicated in the modulation of muscle fiber behavior. We aim to determine whether stretching exercise is protective against reloading-induced muscle damage in immobilized rat soleus muscle. METHODS: Rat hindlimbs in 54 eight-week-old male Wistar rats were immobilized by cast for 4 weeks, followed by reloading alone through normal ambulation in 24 (group NS) and after passive stretch in 25 rats (group S). Stretching exercise (30 min each day) lasted 6 days. To determine if passive stretching affects expression of heat shock proteins (HSPs) in rat soleus muscle during reloading following cast immobilization, the ratio of invading muscle fibers and HSPs expression were measured following cast removal. RESULTS: The ratio of invading muscle fibers increased during the first and second days of reloading in group NS. Compared with reloading alone, stretching exercise reduced invading muscle fibers at most time points following cast removal (group S). Additionally, expression of HSP25 and HSP72 increased with time during reloading only in the group without passive stretch (group NS). CONCLUSION: Following immobilization, in the rat soleus muscle passive stretching exercise protects against injury induced by reloading. Furthermore, the protection provided by passive stretch is independent of HSPs.

Changes in Flexibility and Force are not Different after Static Versus Dynamic Stretching.

In this study, we examined the effects of static and dynamic stretching on range of motion (ROM), passive torque (PT) at pain onset, passive stiffness, and isometric muscle force. We conducted a randomized crossover trial in which 16 healthy young men performed a total of 300 s of active static or dynamic stretching of the right knee flexors on two separate days in random order. To assess the effects of stretching, we measured the ROM, PT at pain onset, passive stiffness during passive knee extension, and maximum voluntary isometric knee flexion force using an isokinetic dynamometer immediately before and after stretching. Both static and dynamic stretching significantly increased the ROM and PT at pain onset (p<0.01) and significantly decreased the passive stiffness and isometric knee flexion force immediately after stretching (p<0.01). However, the magnitude of change did not differ between the two stretching methods for any measurements. Our results suggest that 300 s of either static or dynamic stretching can increase flexibility and decrease isometric muscle force; however, the effects of stretching do not appear to differ between the two stretching methods.