Coordination of plantar flexor muscles during bipedal and unipedal stances in young and elderly adults.

To investigate the effects of aging on coordination of plantar flexor muscles during bipedal and unipedal stances, we examined a relationship between the center of pressure sway and electromyographic activity of these muscles, and also the common neural input, using a coherence analysis. Healthy young and elderly adults were asked to perform bipedal and unipedal standing. The electromyograms were recorded unilaterally from the medial and lateral gastrocnemius (MG and LG) and soleus (SL) muscles, and the common input was analyzed for MG-LG, MG-SL, and LG-SL pairs in two frequency bands: a delta band, that is associated with force variability, and a beta band, that could reflect the corticospinal drive. Main results indicated that the MG and SL muscles worked for lateral sway, while the LG muscle worked for medial sway during the unipedal stance. The delta-band coherence for the MG-SL pair and the beta-band coherences for all the pairs were larger during the unipedal than bipedal stance for both groups. The delta-band coherence for the MG-SL pair was larger for the elderly than young adults during the unipedal stance. In addition, the beta-band coherence for the MG-SL pair was larger than the other pairs during the unipedal stance for the elderly. These findings suggest that the oscillatory activity between the MG and SL muscles is strongly involved in the control of unipedal stance, and aging would increase the cortical drive to these muscles to deal with the postural sway that could be affected by forces generated cooperatively by them.

Behavioral Effect of Short- and Long-Term Exercise on Motor Functional Recovery after Intracerebral Hemorrhage in Rats.

BACKGROUND: In this study, we investigated the effects of short- and long-term exercise on motor functional recovery following intracerebral hemorrhage (ICH) in rats. METHODS: Male Wistar rats were randomly divided into 5 experimental groups: ICH without training (ICH group), ICH with long-term exercise for 14days from the second day after surgery (ICH + LT group), ICH with short-term exercise for 7days from the second day after surgery (ICH + EST group), ICH with short-term exercise for 7days from the ninth day after surgery (ICH + LST group), and sham operation without training (SHAM group). ICH was induced by collagenase injection into the left striatum. Forelimb sensorimotor function was evaluated using forelimb placing and horizontal ladder tests. RESULTS: In the behavioral test, the ICH + LT and ICH + EST groups improved significantly compared with the ICH and ICH + LT groups. The ICH + LT and ICH + EST groups recovered motor function in an almost analogous pattern. CONCLUSIONS: Our results indicated that, when exercise was started from an early phase after ICH, both short- and long-term exercises had similar benefits on motor functional recovery. However, continuous training using simple treadmill running may have limitations to motor functional recovery.

Auditory stimulus has a larger effect on anticipatory postural adjustments in older than young adults during choice step reaction.

PURPOSE: The study aim was to compare the influence of an auditory stimulus (AS) on anticipatory postural adjustments (APAs) between young and older adults during a choice step reaction. METHODS: Sixteen young and 19 older adults stepped forward in response to a visual imperative stimulus of an arrow. We used a choice reaction time (CRT) task and a Simon task which consisted of congruent and incongruent conditions. The direction of the presented arrow and its spatial location matched in the congruent condition while they did not in the incongruent condition. The AS was presented randomly and simultaneously with the visual stimulus. Incorrect weight shifts before lifting off the foot, termed APA errors, stepping errors, temporal parameters, and APA amplitudes were analyzed. RESULTS: The APA error rate was higher in trials with than without AS in all task conditions for the older group, while this increase occurred only in the incongruent condition for the young group. The stepping error rate was also increased in the presence of AS in the incongruent condition for the older group. Reaction times were faster with AS in both groups. The APA amplitude of erroneous APA trials became larger with AS in the incongruent condition for both groups, and this effect appeared greater for the older group. CONCLUSIONS: The effect of AS on APAs is larger in the elderly during a choice step reaction. In the presence of incongruent visual information, this effect becomes even greater, potentially inducing not only APA errors but also stepping errors.

Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

BACKGROUND: We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). METHODS: Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. RESULTS: Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. CONCLUSIONS: These changes may play a critical role in motor skills training-induced recovery after ICH.

Performance monitoring and response conflict resolution associated with choice stepping reaction tasks.

Choice reaction requires response conflict resolution, and the resolution processes that occur during a choice stepping reaction task undertaken in a standing position, which requires maintenance of balance, may be different to those processes occurring during a choice reaction task performed in a seated position. The study purpose was to investigate the resolution processes during a choice stepping reaction task at the cortical level using electroencephalography and compare the results with a control task involving ankle dorsiflexion responses. Twelve young adults either stepped forward or dorsiflexed the ankle in response to a visual imperative stimulus presented on a computer screen. We used the Simon task and examined the error-related negativity (ERN) that follows an incorrect response and the correct-response negativity (CRN) that follows a correct response. Error was defined as an incorrect initial weight transfer for the stepping task and as an incorrect initial tibialis anterior activation for the control task. Results revealed that ERN and CRN amplitudes were similar in size for the stepping task, whereas the amplitude of ERN was larger than that of CRN for the control task. The ERN amplitude was also larger in the stepping task than the control task. These observations suggest that a choice stepping reaction task involves a strategy emphasizing post-response conflict and general performance monitoring of actual and required responses and also requires greater cognitive load than a choice dorsiflexion reaction. The response conflict resolution processes appear to be different for stepping tasks and reaction tasks performed in a seated position.

Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule-Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage.

BACKGROUND: In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. METHODS: Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. RESULTS: Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. CONCLUSIONS: Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex.

Liquid diet induces memory impairment accompanied by a decreased number of hippocampal neurons in mice.

It is suggested that masticatory dysfunction affects the central nervous system; however, the underlying mechanism remains unknown. Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are known to play important roles in memory and learning. In this study, we examined the effects of mastication on memory, the expression levels of BDNF and TrkB, and the number of neurons in the hippocampus of mice. Male C57 BL/6J mice (3 weeks old) were randomly divided into the control group (N = 7) fed chow pellets and the experimental group (N = 7) fed a liquid diet, which reduces mastication during eating. At 14 weeks of age, we performed a passive avoidance test and found that memory and learning ability were impaired in the experimental group compared with the control group. After the behavioral experiment, brains were harvested and analyzed morphologically and biochemically. In the hippocampus of the experimental group, the expression levels of BDNF were significantly higher, whereas those of TrkB were lower than those of the control group. In the cerebral cortex, these levels remained unchanged between the two groups. The ratio of phospho-p44/42 ERK/pan ERK, a downstream molecule of BDNF/TrkB signaling, in the experimental group was significantly lower than that of the control group in the cortex and hippocampus. The number of pyramidal neurons in the hippocampus was lower in the experimental group than in the control group. These findings suggest that reduced mastication induced by a liquid diet in early childhood may impair memory and learning ability, accompanied by neuronal loss in the hippocampus.

Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats.

Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury.

Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo.

Interleukin (IL)-15 is expressed in a variety of inflammatory diseases. However, the contribution of dendritic cell (DC)-derived IL-15 to the development of diseases is uncertain. Using established models of Propionibacterium acnes (P. acnes)- and zymosan-induced liver inflammation, we observed granuloma formation in the livers of wild-type (WT) and RAG-2(-/-) mice but not in those of IL-15(-/-) mice. We demonstrate that this is likely caused by an impaired sequential induction of IL-12, IFN-gamma, and chemokines necessary for monocyte migration. Likewise, lethal endotoxin shock was not induced in P. acnes- and zymosan-primed IL-15(-/-) mice or in WT mice treated with a new IL-15-neutralizing antibody. In both systems, proinflammatory cytokine production was impaired. Surprisingly, neither granuloma formation, lethal endotoxin shock, nor IL-15 production was induced in mice deficient for DCs, and adoptive transfer of WT but not IL-15(-/-) DCs restored the disease development in IL-15(-/-) mice. Collectively, these data indicate the importance of DC-derived IL-15 as a mediator of inflammatory responses in vivo.

Repetitive training of contralateral limb through reconsolidation strengthens motor skills.

Consolidated memories become transiently labile after memory reactivation, allowing update through reconsolidation. Although previous reports have indicated that the effects of post-reactivation training depend on the type of practice, it is unclear whether post-reactivation motor skill training of one limb can enhance the performance of the opposite limb. The present study aimed to investigate whether post-reactivation training (performing an isometric pinch force task) under two different training conditions using the left limb would enhance motor skills of the right limb through reconsolidation. Motor skills were measured in 38 healthy right-handed young adults during three sessions (S): S1 (right-hand training), S2 (memory reactivation and left-hand training 6 h after S1), and S3 (right-hand motor skill test 24 h after S1). Participants were assigned to one of three groups according to the task performed during S2: untrained controls (no training), left-hand training (constant force conditions), or left-hand training (variable force conditions). Left-hand training after memory reactivation during S2 significantly enhanced the motor skills of the right hand. Notably, constant training conditions significantly increased performance compared to the control group. These findings suggest that post-reactivation training in one limb effectively enhances motor skills in the opposite limb, and the effects depend on the training strategy, which has important implications for motor rehabilitation.

Minor neuronal damage and recovered cellular proliferation in the hippocampus after continuous unilateral forelimb restraint in normal rats.

Constraint-induced movement therapy (CIMT) involves the restraint of an intact limb to force the dominant use of an affected limb, in an attempt to enhance use-dependent plasticity and reduce dysfunction. To investigate whether forced disuse of an intact forelimb with CIMT causes a loss of limb function and degenerative damage in the brain, a staircase test and a horizontal ladder test were carried out in control rats and forelimb-restrained rats, and then Argyrophil III silver staining, which is capable of detecting subtle neuronal damage, was used to examine histological alterations associated with restraint. No significant changes in forelimb function were observed in restrained rats. However, atypical weak argyrophilic neurons, an indicator of minor neural damage, were found in the bilateral hippocampus of restrained rats. This damage was not found in the cortex, striatum, or spinal cord. Investigation of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) revealed a clear reduction in the number of bromodeoxyuridine-positive cells in bilateral SGZ, but not in the SVZ, in restrained rats compared with controls. This reduction was accompanied by reduced mRNA expression of vascular endothelial growth factor and glial-derived neurotrophic factor. However, reduced cellular proliferation and decreased gene expression were recovered after the removal of the restraint. Our results suggest that forced disuse of the intact forelimb has no significant effect on skilled forelimb function but has a minor effect on neurogenesis in SGZ, suggesting that mild stress may be caused by the restraint.

IL-15 serves as a costimulator in determining the activity of autoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease.

To elucidate the mechanisms controlling peripheral tolerance, we established two transgenic (Tg) mouse strains expressing different levels of membrane-bound OVA (mOVA) as a skin-associated self-Ag. When we transferred autoreactive TCR-Tg CD8 T cells (OT-I cells), keratin 14 (K14)-mOVA(high) Tg mice developed autoreactive skin disease (graft-vs-host disease (GVHD)-like skin lesions) while K14-mOVA(low) Tg mice did not. OT-I cells in K14-mOVA(high) Tg mice were fully activated with full development of effector function. In contrast, OT-I cells in K14-mOVA(low) Tg mice proliferated but did not gain effector function. Exogenous IL-15 altered the functional status of OT-I cells and concomitantly induced disease in K14-mOVA(low) Tg mice. Conversely, neutralization of endogenous IL-15 activity in K14-mOVA(high) Tg mice attenuated GVHD-like skin lesions induced by OT-I cell transfer. Futhermore, K14-mOVA(high) Tg mice on IL-15 knockout or IL-15Ralpha knockout backgrounds did not develop skin lesions after adoptive transfer of OT-I cells. These results identify IL-15 as an indispensable costimulator that can determine the functional fate of autoreactive CD8 T cells and whether immunity or tolerance ensues, and they suggest that inhibition of IL-15 function may be efficacious in blocking expression of autoimmunity where a breach in peripheral tolerance is suspected.

Fatigue-induced decline in low-frequency common input to bilateral and unilateral plantar flexors during quiet standing.

Plantar flexor muscles play a crucial role in maintaining balance during quiet standing. The purpose of this study was to investigate the effect of their fatigue on common input to these muscles, using a coherence analysis. Thirteen healthy young male adults stood quietly before and after a fatigue protocol consisting of a heel raise exercise. Center of pressure (COP) displacement and electromyograms (EMGs) from the bilateral medial gastrocnemius and soleus muscles were recorded. EMG-EMG coherences between the bilateral homologous muscles (bilateral coherence) and within the unilateral muscles (unilateral coherence) in the right leg were calculated. Anteroposterior and mediolateral COP speeds, mediolateral COP SD, and 95% confidence ellipse area were larger in post- than pre-fatigue condition. Bilateral and unilateral coherences in delta band, that reflect comodulation of muscle activation, and bilateral coherence in alpha band, that is supposedly associated with the subcortical inputs, were smaller in post- than pre-fatigue condition. Unilateral coherences in alpha and beta band, reflecting physiological tremor and corticospinal drive, respectively, were not different between pre- and post-fatigue conditions. It is suggested that the low-frequency common input to the plantar flexor muscles is reduced following the fatiguing contraction during quiet standing, likely by a change in the postural control strategy.

Age-Related Declines in the Ability to Modulate Common Input to Bilateral and Unilateral Plantar Flexors During Forward Postural Lean.

Aging can impair an ability to lean the body forward to the edge of the base of support. Here, we investigated, using a coherence analysis, common inputs to bilateral and unilateral plantar flexor muscles to test a hypothesis that the age-related impairment would be related to strong synchronous bilateral activation and reduced cortical control of these muscles. Healthy young (n = 14) and elderly adults (n = 19), who were all right-foot dominant, performed quiet standing task and tasks that required the subjects to lean their body forward to 35 and 75% of the maximum lean distance. The electromyogram was recorded from the bilateral medial gastrocnemius (MG) and soleus (SL) muscles. We analyzed delta-band coherence, that reflects comodulation of muscle activity, between the bilateral homologous muscles (MG-MG and SL-SL pairs). The origin of this bilateral comodulation is suggested to be the subcortical system. Also, we examined beta-band coherence, that is related to the corticospinal drive, between the unilateral muscles (MG-SL pair) in the right leg. Results indicated that the bilateral delta-band coherence for the MG-MG pair was significantly smaller in the 75% forward lean than quiet standing and 35% forward lean tasks for the young adults (quiet: p = 0.036; 35%: p = 0.0011). The bilateral delta-band coherence for the SL-SL pair was significantly smaller in the 75% forward lean than 35% forward lean task for the young adults (p = 0.027). Furthermore, the unilateral beta-band coherence was larger in the forward lean than quiet standing task for the young adults (35%: p < 0.001; 75%: p = 0.029). Contrarily, the elderly adults did not demonstrate such changes. These findings suggest the importance of decreasing the synchronous bilateral activation and increasing the unilateral cortical control of the plantar flexor muscles for the successful forward postural lean performance, and that aging impairs this modulatory ability.

Effect of auditory stimulus on executive function and execution time during cognitively demanding stepping task in patients with Parkinson's disease.

Start hesitation in patients with Parkinson's disease (PD) occurs predominantly during distractive and conflictual situations. The aim of this study was to investigate how differently an auditory stimulus (AS) influences execution function and execution time during a cognitively demanding stepping task in PD patients as compared to healthy controls. PD patients and healthy controls stepped forward in response to a visual imperative stimulus of an arrow. We applied a Simon task that comprised congruent and incongruent conditions. Direction and location of the arrow matched in the congruent condition, while they didn't in the incongruent condition. AS were randomly and simultaneously presented with the visual stimulus. An error in the direction of an anticipatory postural adjustment (APA), termed an APA error, and temporal parameters (reaction onset of APA and APA duration) were analyzed. As a result, the AS increased the APA error rate in the control group regardless of the condition, but they did not influence it in the PD group. The AS also speeded the reaction onset in both groups regardless of the condition. The APA duration was prolonged by the AS for the control group, while it was unaffected by the AS for the PD group in both conditions. These findings indicate that AS could facilitate a step initiation, conceivably by facilitating a stimulus identification process and increasing attentional control of stepping behavior, without influencing a decision-making process even in a cognitively demanding condition in patients with PD.

Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid ß (Aß) deposition, Aß40, and Aß42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1ß and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis-inoculated mice. P. gingivalis LPS-induced production of Aß40 and Aß42 in neural cell cultures and strongly enhanced TNF-α and IL-1ß production in a culture of microglial cells primed with Aß. Periodontitis evoked by P. gingivalis may exacerbate brain Aß deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.

Running exercise enhances motor functional recovery with inhibition of dendritic regression in the motor cortex after collagenase-induced intracerebral hemorrhage in rats.

Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation.

Preparatory state and postural adjustment strategies for choice reaction step initiation.

A loud auditory stimulus (LAS) presented simultaneously with a visual imperative stimulus can reduce reaction time (RT) by automatically triggering a movement prepared in the brain and has been used to investigate a movement preparation. It is still under debate whether or not a response is prepared in advance in RT tasks involving choice responses. The purpose of the present study was to investigate the preparatory state of anticipatory postural adjustments (APAs) during a choice reaction step initiation. Thirteen young adults were asked to step forward in response to a visual imperative stimulus in two choice stepping conditions: (i) the responding side is not known and must be selected and (ii) the responding side is known but whether to initiate or inhibit a step response must be selected. LAS was presented randomly and simultaneously with the visual imperative stimulus. LAS significantly increased the occurrence rates of inappropriately initiated APAs while reducing the RTs of correct and incorrect trials in both task conditions, demonstrating that LAS triggered the prepared APA automatically. This observation suggests that APAs are prepared in advance and withheld from release until the appropriate timing during a choice reaction step initiation. The preparatory activity of APAs might be modulated by the inhibitory activity required by the choice tasks. The preparation strategy may be chosen for fast responses and is judged most suitable to comply with the tasks because inappropriately initiated APAs can be corrected without making complete stepping errors.

Differential contribution of clinical amounts of acetaldehyde to skeletal and cardiac muscle dysfunction in alcoholic myopathy.

Acute intoxication due to alcohol consumption has been known to elicit reversible skeletal and cardiac muscle dysfunction, or "alcoholic myopathy and cardiomyopathy". Sometimes, irreversible muscle damage can be induced after heavy alcohol drinking. Many researchers have proposed that acetaldehyde, the major oxidised product of alcohol, may be a primary factor underlying alcohol-induced muscle dysfunction. Because acetaldehyde is rapidly metabolised to acetate by aldehyde dehydrogenase (ALDH) mainly in the liver, blood concentration of acetaldehyde is maintained at a low level even after heavy alcohol intoxication. In alcoholics, blood acetaldehyde level is relatively high, probably due to hepatic inhibition of ALDH activity. Several mM of acetaldehyde have been used for studies of cardiac muscle contraction, the intracellular calcium transient, and the L-type calcium channel. In skeletal muscle, the calcium release channel/ryanodine receptor activity has been reported to be inhibited by exposure to 1 mM acetaldehyde. However, these observations were made using potentially lethal concentrations of acetaldehyde, so the hypothesis that acetaldehyde plays a crucial role on alcoholic myopathy is questionable. In this review, we will summarise the effect of alcohol and its major oxidised product, acetaldehyde, on skeletal and heart muscles and propose a toxic contribution of clinical concentrations of acetaldehyde to alcoholic myopathy. In addition, this review will include briefly the effect of acetaldehyde on diabetic cardiomyopathy.

Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat.

Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion. Recovery of forelimb function in the skilled reaching test and the ladder stepping test was found after early-CIMT, while no significant recovery was shown after late CIMT or in the non-CIMT controls. Early CIMT was associated with greater numbers of ΔFosB-positive cells in the ipsi-lesional sensorimotor cortex layers II-III and V. Additionally, we found expression of the growth-related genes brain-derived neurotrophic factor (BDNF) and growth-related protein 43 (GAP-43), and abundant dendritic arborization of pyramidal neurons in the sensorimotor area. Similar results were not detected in the contra-lesional cortex. In contrast to early CIMT, late CIMT failed to induce any changes in plasticity. We conclude that CIMT induces molecular and morphological plasticity in the ipsi-lesional sensorimotor cortex and facilitates better functional recovery when initiated immediately after hemorrhage.