Separated center-of-pressure measurements reveal new characteristics of reduced anticipatory postural adjustments during gait initiation in patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Accelerations, ground reaction force data, and other quantitative data obtained from kinematic analyses of gait initiation serve as measures of dyskinesia in patients with Parkinson's disease. The objective of this study was to determine whether a separate center of pressure information could reveal new characteristics of reduced anticipatory postural adjustments in patients with Parkinson's disease. METHODS: Ten healthy elderly subjects and 10 patients with Parkinson's disease participated in this study. Motions at gait initiation in response to a light signal to begin the task were analyzed. Anticipatory postural adjustments were characterized using trunk acceleration data and center of pressure displacement data. RESULTS: The separated center of pressure in patients with Parkinson's disease showed longer peak latency (p < .01) and larger peak magnitude (p < .01) in the stance leg than in the stepping leg. In patients with Parkinson's disease, the displacement peak latency of the stance leg center of pressure correlated negatively with the Timed Up and Go time (r = -0.46, p < .05), while displacement peak latency of the stepping leg center of pressure correlated negatively with Unified Parkinson's Disease Rating Scale (r=  -0.47, p < .05), and positively with Berg Balance Scale score (r = 0.50, p < .05). CONCLUSIONS: Patients with Parkinson's disease experience asymmetry between the stance leg and stepping leg at gait initiation. These findings may help clinicians understand the changes to motor function in patients with Parkinson's disease and suggest strategies for improved rehabilitation training.

Gait speed and pain status as discriminatory factors for instrumental activities of daily living disability in older adults with knee osteoarthritis.

AIM: Factors related to instrumental activities of daily living disability in older adults with knee osteoarthritis are unclear. This study aimed to examine the discriminatory accuracy for the presence of instrumental activities of daily living disability in older adults with knee osteoarthritis by combining two factors of gait ability and pain status. METHODS: A cross-sectional study was conducted on 114 patients with knee osteoarthritis aged ≥ 65 years. Participants were divided into instrumental activities of daily living disabled or non-disabled groups. A logistic regression model was created with usual gait speed and knee injury and osteoarthritis outcome score-pain subscale as independent variables for discriminating the presence of instrumental activities of daily living disability. The area under the receiver operating characteristic curve was inspected to determine discriminatory accuracy of the logistic regression model, usual gait speed, knee injury and osteoarthritis outcome score-pain subscale. RESULTS: Of the 114 patients, 26 (22.8%) had instrumental activities of daily living disability. The area under the curves was 0.91 (95% confidence interval: 0.85-0.96) for the logistic regression model, 0.78 (95% confidence interval: 0.68-0.89) for usual gait speed, and 0.73 (95% confidence interval: 0.61-0.84) for knee injury and osteoarthritis outcome score-pain subscale. CONCLUSIONS: This study showed that gait speed and pain status were independent discriminatory factors and combining these factors to discriminate more accurately the presence or absence of instrumental activities of daily living disability in older adults with knee osteoarthritis was important. Geriatr Gerontol Int 2021; 21: 683-688.

Measurements of the centre of pressure of individual legs reveal new characteristics of reduced anticipatory postural adjustments during gait initiation in patients with post-stroke hemiplegia.

OBJECTIVES: To determine whether individual measurements of the centre of pressure for the stance and stepping legs can reveal new characteristics of reduced anticipatory postural adjustments during gait initiation in post-stroke hemiplegic patients. METHODS: Subjects included 30 stroke patients and 10 healthy age-matched controls. The acceleration of the trunk, and the centre of pressure of each leg, were measured during gait initiation, 3 times each with the paretic and non-paretic legs leading. Anticipatory postural adjustments were characterized using trunk acceleration and centre of pressure displacement data. RESULTS: Latency of the posterior displacement peak of the paretic leg centre of pressure with either the paretic or non-paretic leg leading was significantly longer in stroke patients compared with controls, and was also longer than that of the non-paretic leg. The magnitude of the posterior displacement peak of the paretic leg centre of pressure was smaller than that of the non-paretic leg. Peak latency of the paretic stepping leg centre of pressure correlated with the clinical measures of motor dysfunction, postural balance, and gait ability. CONCLUSION: Measurements of the latency and magnitude of centre of pressure displacement peak individually for the paretic and non-paretic legs can help elucidate the mechanism behind reduced anticipatory postural adjustments. This information will be useful in designing new treatment strategies for stroke patients.

Effect of exercise therapy combined with branched-chain amino acid supplementation on muscle strength in elderly women after total hip arthroplasty: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Many patients develop a prolonged decrease of muscle strength after total hip arthroplasty (THA) despite their reconstructed hip joint. Physical exercise combined with branched-chain amino acid (BCAA) supplementation has been reported to improve muscle strength in elderly persons with sarcopenia. However, the effect of BCAA supplementation in patients after THA is unknown. This study examined the effects of BCAA supplementation combined with exercise therapy on the improvement of physical function in elderly patients after THA. METHODS AND STUDY DESIGN: The subjects were 31 elderly women who underwent THA. The participants were randomly assigned to two groups: BCAA (n=18) and control (n=13). The combined therapy was carried out for one month after THA. For the exercise intervention, a 3-set physical exercise program was conducted. For the nutritional intervention, the participants consumed 3.4 g of BCAA supplement or 1.2 g of starch immediately after the exercise intervention. RESULTS: BCAA supplementation combined with muscle strengthening exercises had a significant effect on knee extension strength of the contralateral side and on upper arm cross-sectional area. The improvement ratio of knee extension strength before and after intervention on the operated side was also significantly higher in the BCAA group. CONCLUSIONS: BCAA supplementation is effective for patients to improve the strength of some muscles when combined with physical exercises, but hip abductor muscle strength of the operated leg did not improve. A future study is needed to determine the efficacy of this combined therapy for hip abductor muscle strength.

Effect of exercise therapy combined with branched-chain amino acid supplementation on muscle strengthening in persons with osteoarthritis.

BACKGROUND: Improving lower limb muscle strength is important in preventing progression of osteoarthritis (OA) and its symptoms. Exercise with branched-chain amino acid (BCAA) supplementation has been reported to affect protein anabolism in young and elderly persons. However, few studies provided daily BCAAs for patients with OA. OBJECTIVE: This study examined the effects of combined BCAAs and exercise therapy on physical function improvement in women with hip OA scheduled for total hip arthroplasty. METHODS: The subjects were 43 women with OA (age: 64.2 ± 9.4). The participants were randomly divided into two groups: BCAA ( n = 21 ) and control ( n = 22 ). The combined therapy was carried out for one month. Exercise intervention involved hip abductor muscle exercise in both groups. For the nutritional intervention, 6 g of BCAAs or 1.2 g of starch were consumed within 10 min before starting the exercise. RESULTS: There was a marginally significant difference in the main effect between the groups in 10-m timed gait time. The improvement rate in hip abductor muscle strength of the contralateral side was significantly greater in the BCAA group. CONCLUSION: By combining BCAA intake and exercise therapy, a significant improvement in hip abductor muscle strength of the contralateral side was achieved in women with OA.

Hip, knee, and ankle kinematics during activities of daily living: a cross-sectional study.

BACKGROUND: Joint angle data from healthy subjects are necessary as baseline information. OBJECTIVE: To analyze the problems of patients who struggle with activities of daily living (ADL) due to restricted range of motion and to provide ADL guidance based on objective data. METHOD: An electromagnetic three-dimensional tracking system (FASTRAK) was used to quantify the hip, knee, and ankle angles of the dominant leg of 26 healthy adults as they performed 22 ADLs related to dressing, using the toilet, bathing, picking up objects, and crouching. For each ADL, the maximum angle was averaged across the 26 subjects. Mean angles of adduction/abduction and internal/external rotation during maximum hip flexion were also measured. RESULTS: The largest mean maximum angle was 101° for hip flexion (trunk rotation during crouching), 17° for hip adduction (putting on shoes), and 149° for knee flexion (trunk rotation during crouching). Analysis of adduction/abduction and internal/external rotation angles during maximum hip flexion showed the largest angle of adduction when putting on shoes, and the largest angle of internal rotation with trunk rotation during crouching. CONCLUSIONS: ADLs such as crouching and putting on pants showed larger joint angles than walking, climbing stairs, and standing up. Results obtained from this study can provide important objective data for ADL guidance for total hip arthroplasty and femoroacetabular impingement patients.

Effects of perioperative factors and hip geometry on hip abductor muscle strength during the first 6 months after anterolateral total hip arthroplasty.

[Purpose] The importance and effect of hip joint geometry on hip abductor muscle strength are well known. In addition, other perioperative factors are also known to affect hip abductor muscle strength. This study examined the relative importance of factors affecting hip abductor muscle strength after total hip arthroplasty. [Subjects and Methods] The subjects were 97 females with osteoarthritis scheduled for primary unilateral THA. The following variables were assessed preoperatively and 2 and 6 months after surgery: isometric hip abductor strength, radiographic analysis (Crowe class, postoperative femoral offset (FO)), Frenchay Activities Index, compliance rate with home exercise, Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), and demographic data. Factors related to isometric hip abductor muscle strength 2 and 6 months after surgery were examined. [Results] Significant factors related to isometric hip abductor muscle strength at 2 and 6 months after surgery were, in extraction order: 1. isometric hip abductor muscle strength in the preoperative period; 2. BMI; and 3. the JHEQ mental score at 2 and 6 months after surgery. [Conclusion] Preoperative factors and postoperative mental status were related to postoperative isometric hip abductor strength. FO was not extracted as a significant factor related to postoperative isomeric hip abductor strength.

Correlations between sagittal plane kinematics and landing impact force during single-leg lateral jump-landings.

[Purpose] The correlations of peak vertical ground reaction force and sagittal angles during single-leg lateral jump-landing with noncontact anterior cruciate ligament injury remain unknown. This study aimed to clarify the correlations between kinematics and impact force during lateral jump-landing. [Subjects and Methods] Twenty active males were included in the analysis. A sagittal-view movie camera and force plate were time synchronized. Trunk and lower extremity sagittal angles were measured 100 ms before initial contact and at peak vertical ground reaction force. Peak vertical ground reaction force, time between initial contact and peak vertical ground reaction force, and loading rate were calculated. [Results] The mean sagittal angle was 40.7° ± 7.7° for knee flexion during the flight phase and 16.4° ± 6.3° for pelvic anterior inclination during the landing phase. The mean peak vertical ground reaction force was four times the body weight. The median time to peak vertical ground reaction force was 63.8 ms. The knee flexion during the flight phase and pelvic anterior inclination angles during the landing phase were related to the peak vertical ground reaction force. [Conclusion] Increasing knee flexion and decreasing pelvic anterior inclination might reduce the impact during single-leg lateral jump-landing.

Effects and feasibility of exercise therapy combined with branched-chain amino acid supplementation on muscle strengthening in frail and pre-frail elderly people requiring long-term care: a crossover trial.

This study examined the effects and feasibility of a twice-weekly combined therapy of branched-chain amino acids (BCAAs) and exercise on physical function improvement in frail and pre-frail elderly people requiring long-term care. We used a crossover design in which the combination of exercise and nutritional interventions was carried out twice a week during cycles A (3 months) and B (3 months) and the exercise intervention alone was performed during the washout period. The exercise intervention entailed the following 5 training sets: 3 sets of muscle training at 30% of maximum voluntary contraction, 1 set of aerobic exercise, and 1 set of balance training. For the nutritional intervention, 6 g of BCAAs or 6 g of maltodextrin was consumed 10 min before starting the exercise. We determined upper and lower limb isometric strength, performance on the Functional Reach Test (FRT) and the Timed Up and Go test, and activity level. In the comparison between the BCAA group and the control group after crossover, the improvement rates in gross lower limb muscle strength (leg press, knee extension) and FRT performance were significantly greater (by approximately 10%) in the BCAA group. In the comparison between different orders of BCAA administration, significant effects were shown for the leg press in both groups only when BCAAs were given. The combination of BCAA intake and exercise therapy yielded significant improvements in gross lower limb muscle strength and dynamic balance ability.

Incidence of floating toe and its association with the physique and foot morphology of Japanese children.

[Purpose] Physical development, foot morphology, and toe contact of children aged 3 to 5 years were assessed in order to investigate the relationships between body and foot morphology and the incidence of the condition known as "floating toe". [Subjects] A total of 198 children, aged 3 to 5 years old, participated in this study. [Methods] Height and weight were measured for body morphology, and foot length and width were measured for foot morphology. Footprint images were taken to calculate the number of floating toes. Information about the children's height and weight at birth, and the time of starting to walk was obtained from their guardians. [Results] At least one floating toe was observed in 87.7-98.7% of the children depending on their ages. The fifth toe was most commonly affected, occurring in 74.2% of the study population. Among the body and foot morphology parameters, only weight at birth showed a significant but very weak correlation with the number of floating toes. [Conclusion] There was a high incidence of floating toe among the children, with the fifth toe most commonly affected. Floating toe weakly but significantly correlated with weight at birth, but did not correlated with other measures of physique at birth, physical development, or the time of starting to walk.

Molecular dynamics simulation for the reversed power stroke motion of a myosin subfragment-1.

Myosins are typical molecular motor proteins that convert the chemical energy from the ATP hydrolysis into mechanical work. The fundamental mechanism of this energy conversion is still unknown. To explain the experimental results already obtained, Masuda has proposed a hypothesis called the "Driven by Detachment" theory for the working principle of the myosins. This theory insists that the energy used during the power stroke of the myosins does not directly originate from the chemical energy of ATP, but is converted from the elastic energy within the molecule at the joint between the head and neck domains. One method for demonstrating the validity of this theory is a computational simulation using the molecular dynamics (MD) method. The MD software used was GROMACS. The target of the MD simulations was myosin subfragment-1 (S1), for which the initial structure was obtained from the Protein Data Bank entry 1M8Q. The AFM pull code of GROMACS was used to apply an external force of 17 pN at the end of the neck domain in the direction opposite to the power stroke to observe whether the myosin S1 takes the pre-power stroke conformation. The residues assumed to be engaged in the docking with an actin filament were fixed to the space. Starting from exactly the same initial position, 10 simulations were repeated by varying the random seeds for generating the initial velocities of the atoms. After 64ns of calculations, the myosin S1 took the conformation of the pre-power stroke state in which the neck domain was bent around the joint between the head and the neck domains. This result agrees with the prediction expected by the DbD theory, the validity of which may be established by conducting similar simulations for the other steps of the myosin working processes.

Enhanced electrical responsiveness in the cerebral cortex with oral melatonin administration after a small hemorrhage near the internal capsule in rats.

Intracerebral hemorrhage (ICH) can cause direct brain injury at the insult site and indirect damage in remote brain areas. Although a protective effect of melatonin (ML) has been reported for ICH, its detailed mechanisms and effects on remote brain injury remain unclear. To clarify the mechanism of indirect neuroprotection after ICH, we first investigated whether ML improved motor function after ICH and then examined the underlying mechanisms. The ICH model rat was made by collagenase injection into the left globus pallidus, adjacent to the internal capsule. ML oral administration (15 mg/kg) for 7 days after ICH resulted in significant recovery of motor function. Retrograde labeling of the corticospinal tract by Fluoro-Gold revealed a significant increase in numbers of positive neurons in the cerebral cortex. Immunohistological analysis showed that ML treatment induced no difference in OX41-positive activated microglia/macrophage at day 1 (D1) but a significant reduction in 8-hydroxydeoxyguanosin-positive cells at D7. Neutral red assay revealed that ML significantly prevented H2 O2 -induced cell death in cultured oligodendrocytes and astrocytes but not in neurons. Electrophysiological response in the cerebral cortex area where the number of Fluoro-Gold-positive cells was increased was significantly improved in ML-treated rats. These data suggest that ML improves motor abilities after ICH by protecting oligodendrocytes and astrocytes in the vicinity of the lesion in the corticospinal tract from oxidative stress and causes enhanced electrical responsiveness in the cerebral cortex remote to the ICH pathology.

Analysis of L-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli.

BACKGROUND: Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. RESULTS: We constructed an L-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for L-glutamic acid production; the results of this process corresponded with previous experimental data regarding L-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of L-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model L-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in L-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. CONCLUSIONS: In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation.

Ranges of active joint motion for the shoulder, elbow, and wrist in healthy adults.

PURPOSE: The aim of this study was to show highly reliable normal values and three-dimensional characteristics for final range of motion during active movements of the upper extremity joints, and to develop a database from healthy participants, with the advantage of this database lying in the methods of defining shoulder axial rotation angle and of compensating for soft tissue artifacts. METHODS: We used an electromagnetic tracking system (FASTRAK) to measure three-dimensional motions of the shoulder (thoracohumeral), elbow/forearm, and wrist in 20 healthy adults (age range: 18-34 years) during active joint motion tasks of the upper extremity. RESULTS: Joint angles of the upper extremity at the final position of joint motion tasks were determined. Highly reliable data for shoulder axial rotation angle were obtained, using a new definition of joint angle and regression analysis to compensate for estimation errors. CONCLUSIONS: These results should be useful in setting goals for the treatment of upper extremity joint functions in the fields of rehabilitation, orthopedics, and sports medicine.

Molecular dynamics simulation of a myosin subfragment-1 docking with an actin filament.

Myosins are typical molecular motor proteins, which convert the chemical energy of ATP into mechanical work. The fundamental mechanism of this energy conversion is still unknown. To explain the experimental results observed in molecular motors, Masuda has proposed a theory called the "Driven by Detachment (DbD)" mechanism for the working principle of myosins. Based on this theory, the energy used during the power stroke of the myosins originates from the attractive force between a detached myosin head and an actin filament, and does not directly arise from the energy of ATP. According to this theory, every step in the myosin working process may be reproduced by molecular dynamics (MD) simulations, except for the ATP hydrolysis step. Therefore, MD simulations were conducted to reproduce the docking process of a myosin subfragment-1 (S1) against an actin filament. A myosin S1 directed toward the barbed end of an actin filament was placed at three different positions by shifting it away from the filament axis. After 30 ns of MD simulations, in three cases out of ten trials on average, the myosin made a close contact with two actin monomers by changing the positions and the orientation of both the myosin and the actin as predicted in previous studies. Once the docking was achieved, the distance between the myosin and the actin showed smaller fluctuations, indicating that the docking is stable over time. If the docking was not achieved, the myosin moved randomly around the initial position or moved away from the actin filament. MD simulations thus successfully reproduced the docking of a myosin S1 with an actin filament. By extending the similar MD simulations to the other steps of the myosin working process, the validity of the DbD theory may be computationally demonstrated.

Evolution of neuronal and astroglial disruption in the peri-contusional cortex of mice revealed by in vivo two-photon imaging.

In traumatic brain injury mechanical forces applied to the cranium and brain cause irreversible primary neuronal and astroglial damage associated with terminal dendritic beading and spine loss representing acute damage to synaptic circuitry. Oedema develops quickly after trauma, raising intracranial pressure that results in a decrease of blood flow and consequently in cerebral ischaemia, which can cause secondary injury in the peri-contusional cortex. Spreading depolarizations have also been shown to occur after traumatic brain injury in humans and in animal models and are thought to accelerate and exacerbate secondary tissue injury in at-risk cortical territory. Yet, the mechanisms of acute secondary injury to fine synaptic circuitry within the peri-contusional cortex after mild traumatic brain injury remain unknown. A mild focal cortical contusion model in adult mouse sensory-motor cortex was implemented by the controlled cortical impact injury device. In vivo two-photon microscopy in the peri-contusional cortex was used to monitor via optical window yellow fluorescent protein expressing neurons, enhanced green fluorescent protein expressing astrocytes and capillary blood flow. Dendritic beading in the peri-contusional cortex developed slowly and the loss of capillary blood flow preceded terminal dendritic injury. Astrocytes were swollen indicating oedema and remained swollen during the next 24 h throughout the imaging session. There were no recurrent spontaneous spreading depolarizations in this mild traumatic brain injury model; however, when spreading depolarizations were repeatedly induced outside the peri-contusional cortex by pressure-injecting KCl, dendrites undergo rapid beading and recovery coinciding with passage of spreading depolarizations, as was confirmed with electrophysiological recordings in the vicinity of imaged dendrites. Yet, accumulating metabolic stress resulting from as few as four rounds of spreading depolarization significantly added to the fraction of beaded dendrites that were incapable to recover during repolarization, thus facilitating terminal injury. In contrast, similarly induced four rounds of spreading depolarization in another set of control healthy mice caused no accumulating dendritic injury as dendrites fully recovered from beading during repolarization. Taken together, our data suggest that in the mild traumatic brain injury the acute dendritic injury in the peri-contusional cortex is gated by the decline in the local blood flow, most probably as a result of developing oedema. Furthermore, spreading depolarization is a specific mechanism that could accelerate injury to synaptic circuitry in the metabolically compromised peri-contusional cortex, worsening secondary damage following traumatic brain injury.

Cross-cultural differences in the processing of non-verbal affective vocalizations by Japanese and canadian listeners.

The Montreal Affective Voices (MAVs) consist of a database of non-verbal affect bursts portrayed by Canadian actors, and high recognitions accuracies were observed in Canadian listeners. Whether listeners from other cultures would be as accurate is unclear. We tested for cross-cultural differences in perception of the MAVs: Japanese listeners were asked to rate the MAVs on several affective dimensions and ratings were compared to those obtained by Canadian listeners. Significant Group × Emotion interactions were observed for ratings of Intensity, Valence, and Arousal. Whereas Intensity and Valence ratings did not differ across cultural groups for sad and happy vocalizations, they were significantly less intense and less negative in Japanese listeners for angry, disgusted, and fearful vocalizations. Similarly, pleased vocalizations were rated as less intense and less positive by Japanese listeners. These results demonstrate important cross-cultural differences in affective perception not just of non-verbal vocalizations expressing positive affect (Sauter et al., 2010), but also of vocalizations expressing basic negative emotions.

The effect of mastication on reaction latency to unanticipated external disturbances in the standing position.

Previous research has shown that mastication reduces shifts in the center of gravity of persons standing still. The present research was conducted to determine whether mastication improves reactive balance in the standing position in response to unanticipated external disturbances. The subjects were 32 healthy male adults (mean age 21.1 years, standard deviation (SD) 0.7 years). Latency data determined with the Motor Control Test of Computerized Dynamic Posturography (CDP) were compared for the three conditions of mastication status, the direction of translation, and the magnitude of translation, using three-way repeated measures ANOVA and lower-order ANOVA with the three conditions separated. Latency was significantly shorter with mastication than with the lower jaw relaxed (P < 0.00001). Mastication alone, however, cannot be considered significant because of the complex interactions involved among the three conditions. Mastication increases not only static balance but also reactive balance in response to unanticipated external disturbances. Gum chewing may therefore reduce falls among elderly persons with impaired balance.

Capillary blood flow around microglial somata determines dynamics of microglial processes in ischemic conditions.

Microglia are the resident immune cells in the brain. Under normal conditions, resting ramified microglia constantly extend and retract fine processes while performing immunological surveillance. In ischemia, microglia become activated as demonstrated by morphological changes during deramification leading to transformation from ramified to amoeboid form. In vivo two-photon microscopy of enhanced green fluorescent protein (EGFP)-expressing microglia in mouse neocortex was used to examine microglial dynamics during the early periods of focal and global ischemia. A penumbra-like "area-at-risk" surrounded by a square-shaped area of severely hypoperfused tissue was created by laser-induced photothrombosis. The dynamics of microglial processes in the area-at-risk was strongly correlated with capillary blood flow (BF) measured within 10 µm of microglial somata. Changes in BF around distal microglial processes (>30 µm from somata) had no effect on microglial dynamics. A severe reduction of capillary BF near somata by 84% ± 6% resulted in initiation of microglial deramification, suggesting activation. A moderate decrease in BF near somata by 22% ± 5% or increase by 87% ± 10%, reflecting a redistribution of capillary BF, had no effect on microglial morphology. Complete BF loss during cardiac arrest (CA) or transient bilateral common carotid artery occlusion (BCCAO) entirely stalled all microglial processes without structural changes. Reperfusion after BCCAO induced recovery of microglial dynamics to preocclusion values. These findings suggest that during ischemia, the severe drop in BF around microglial somata coincides with morphological activation. However, this activation requires some residual BF, because complete perfusion loss (as during BCCAO and CA) did not support microglial deramification.

Early onset of forced impaired forelimb use causes recovery of forelimb skilled motor function but no effect on gross sensory-motor function after capsular hemorrhage in rats.

Intensive use of the impaired forelimb promotes behavioral recovery and induces plastic changes of the central nervous system after stroke. However, the optimal onset of intensive use treatment after stroke is controversial. In this study, we investigated whether early forced impaired limb use (FLU) initiated 24h after intracerebral hemorrhage (ICH) of the internal capsule affected behavioral recovery and histological damage. Rats were subjected to ICH via low-dose collagenase infusion or sham stroke. One day after surgery, the ipsilateral forelimbs of half of the ICH and sham rats were casted for a week to induce the use of their contralateral forelimbs. Behavioral assessments were performed on days 10-12 and 26-28 after the surgery and followed by histological assessments. Improvements in skilled reaching and coordinated stepping function were found in the FLU-treated group in comparison with the untreated group after ICH. Additionally, FLU-treated ICH animals showed more normal and precise reaching and stepping movements as compared with ICH control animals. In contrast, FLU did not have a significant impact on gross sensory-motor functions such as the motor deficit score, contact placing response and spontaneous usage of the impaired paw. The volume of tissue lost and the number of spared corticospinal neurons in lesioned motor cortex were not affected by early FLU after ICH. These findings demonstrate the efficacy of early focused use of an impaired limb after internal capsule hemorrhage.