Histone deacetylase expression in white matter oligodendrocytes after stroke

Histone deacetylases (HDACs) constitute a super-family of enzymes grouped into four major classes (Class I–IV) that deacetylate histone tails leading to chromatin condensation and gene repression. Whether stroke-induced oligodendrogenesis is related to the expression of individual HDACs in the oligodendrocyte lineage has not been investigated. We found that 2 days after stroke, oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (OLGs) were substantially reduced in the peri-infarct corpus callosum, whereas at 7 days after stroke, a robust increase in OPCs and OLGs was observed. Ischemic brains isolated from rats sacrificed 7 days after stroke were used to test levels of individual members of Class I (1 and 2) and Class II (4 and 5) HDACs in white matter oligodendrocytes during stroke-induced oligodendrogenesis. Double immunohistochemistry analysis revealed that stroke substantially increased the number of NG2+ OPCs with nuclear HDAC1 and HDAC2 immunoreactivity and cytoplasmic HDAC4 which were associated with augmentation of proliferating OPCs, as determined by BrdU and Ki67 double reactive cells after stroke. A decrease in HDAC1 and an increase in HDAC2 immunoreactivity were detected in mature adenomatous polyposis coli (APC) positive OLGs, which paralleled an increase in newly generated BrdU positive OLGs in the peri-infarct corpus callosum. Concurrently, stroke substantially decreased the acetylation levels of histones H3 and H4 in both OPCs and OLGs. Taken together, these findings demonstrate that stroke induces distinct profiles of Class I and Class II HDACs in white matter OPCs and OLGs, suggesting that the individual members of Class I and II HDACs play divergent roles in the regulation of OPC proliferation and differentiation during brain repair after stroke.     

Stroke-attributable death among older persons during the great recession

Epidemiological evidence indicates an elevated risk for stroke among stressed persons, in general, and among individuals who have lost their job, in particular. We, therefore, tested the hypothesis that stroke accounted for a larger fraction of deaths during the Great Recession than expected from other deaths and from trends, cycles, and other forms of autocorrelation. Based on vital statistics death data from California spanning 132 months from January 2000 through December 2010, we found support for the hypothesis. These findings appear attributable to non-Hispanic white men, who experienced a 5% increase in their monthly odds of stroke-attributable death. Total mortality in this group, however, did not increase. Findings suggest that 879 deaths among older white men shifted from other causes to stroke during the 36 months following the start of the Great Recession. We infer the Great Recession may have affected social, biologic, and behavioral risk factors that altered the life histories of older white men in ways that shifted mortality risk toward stroke.     

Espasticidad tras ictus: ¿la edad es un factor de riesgo? Estudio observacional de la espasticidad en pacientes neurovasculares en una serie retrospectiva de dos centros

ObjectiveApproximately one third of patients who have suffered a stroke develop spasticity. Since clinical observations that spasticity in the elderly population is lower after stroke, and disagreement about risk factors between different authors, an analysis is performed on the variables that influence the development of spasticity.The objective of the study is to determine the how many factors influence spasticity outcome, and the prevalence of spasticity in patients who have suffered a stroke and require intensive rehabilitation treatment.MethodA retrospective assessment was carried out on a total of 554 patients from two neurorehabilitation centres. A record was made of sociodemographic data, aetiology, type and location of stroke, motor and sensory deficits, language and swallowing impairment, incontinence, cognitive and mood state. Spasticity levels at admission and at the third month were studied in 462 patients using the Ashworth scale. Multivariate regression analyses were used to assess the risk factors for spasticity present at the third month after stroke.ResultsThe mean age of the patients was 67.3 years, of which 67.1% were men, and with ischemic aetiology in 76.5%. On admission 31.4% of patients had spasticity, and this increased to 54.8% at the 3^rd month. The absolute risk factor for spasticity was motor index (OR 1.04; 95% CI 1.03-1.05). When this factor was omitted, the variables with predictive ability were: age less than 75 years (OR 0.52; 95% CI 0.30-0.90), sensory impairment (OR 0.66; 95% CI 0.37-1.20), and lower Barthel index score (OR 1.02; 95% CI 1.01-1.03). There was no significant relationship for gender, physiopathological mechanism (ischaemic/haemorrhagic), stroke location, aphasia, or cognitive impairment.ConclusionThe prevalence of spasticity in stroke at third month of follow-up was 54.8%. Motor index is the independent predictor of spasticity. Patients younger than 75 years old, with sensory impairment and low Barthel index score are more likely to develop spasticity.     

Changes in lower limb muscle activity after walking on a split-belt treadmill in individuals post-stroke

Background: There is growing evidence that stroke survivors can adapt and improve step length symmetry in the context of split-belt treadmill (SBT) walking. However, less knowledge exists about the strategies involved for such adaptations. This study analyzed lower limb muscle activity in individuals post-stroke related to SBT-induced changes in step length. Methods: Step length and surface EMG activity of six lower limb muscles were evaluated in individuals post-stroke (n = 16) during (adaptation) and after (after-effects) walking at unequal belt speeds. Results: During adaptation, significant increases in EMG activity were mainly found in proximal muscles (p ⩽ 0.023), whereas after-effects were observed particularly in the distal muscles. The plantarflexor EMG increased after walking on the slow belt (p ⩽ 0.023) and the dorsiflexors predominantly after walking on the fast belt (p ⩽ 0.017) for both, non-paretic and paretic-fast conditions. Correlation analysis revealed that after-effects in step length were mainly associated with changes in distal paretic muscle activity (0.522 ⩽ r ⩽ 0.663) but not with functional deficits. Based on our results, SBT walking could be relevant for training individuals post-stroke who present shorter paretic step length combined with dorsiflexor weakness, or individuals with shorter nonparetic step length and plantarflexor weakness.     

Electromyographic analysis of upper limb muscles during standardized isotonic and isokinetic robotic exercise of spastic elbow in patients with stroke

Although it has been reported that strengthening exercise in stroke patients is beneficial for their motor recovery, there is little evidence about which exercise method is the better option. The purpose of this study was to compare isotonic and isokinetic exercise by surface electromyography (EMG) analysis using standardized methods.Nine stroke patients performed three sets of isotonic elbow extensions at 30% of their maximal voluntary isometric torque followed by three sets of maximal isokinetic elbow extensions with standardization of mean angular velocity and the total amount of work for each matched set in two strengthening modes. All exercises were done by using 1-DoF planner robot to regulate exact resistive torque and speed. Surface electromyographic activity of eight muscles in the hemiplegic shoulder and elbow was recorded. Normalized root mean square (RMS) values and co-contraction index (CCI) were used for the analysis.The isokinetic mode was shown to activate the agonists of elbow extension more efficiently than the isotonic mode (normalized RMS for pooled triceps: 96.0 ± 17.0 (2nd), 87.8 ± 14.4 (3rd) in isokinetic, 80.9 ± 11.0 (2nd), 81.6 ± 12.4 (3rd) in isotonic contraction, F[1, 8] = 11.168; P = 0.010) without increasing the co-contraction of muscle pairs, implicating spasticity or synergy.     

Motor unit number estimation and quantitative needle electromyography in stroke patients

ObjectiveTo evaluate the effect of upper motor neuron damage upon motor units’ function by means of two separate and supplementary electrophysiological methods.MethodsThe abductor digiti minimi muscle of the non-paretic and the paretic side was studied in forty-six stroke patients with (a) motor unit number estimation (MUNE) – adapted multiple point stimulation method and (b) computerized quantitative needle electromyography (EMG) assessing the configuration of voluntary recruited motor unit potentials. Main outcome comparisons were focused on differences between non-paretic and paretic side.ResultsOn the affected hands mean MUNE value was significantly lower and mean area of the surface recorded single motor unit potentials was significantly larger than the corresponding ones on the non-paretic hands. EMG findings did not reveal remarkable differences between the two sides. Neither severity nor chronicity of stroke was related to MUNE or EMG parameters.DiscussionMUNE results, which suggested reduced motor unit numbers in stroke patients, in conjunction with the normal EMG features in these same muscles has given rise to different interpretations. In a clinical setting, reinnervation type changes in the EMG similar to that occurring in neuronopathies or axonal neuropathies should not be expected in muscles with central neurogenic lesion.     

Hip circumduction is not a compensation for reduced knee flexion angle during gait

It has long been held that hip abduction compensates for reduced swing-phase knee flexion angle, especially in those after stroke. However, there are other compensatory motions such as pelvic obliquity (hip hiking) that could also be used to facilitate foot clearance with greater energy efficiency. Our previous work suggested that hip abduction may not be a compensation for reduced knee flexion after stroke. Previous study applied robotic knee flexion assistance in people with post-stroke Stiff-Knee Gait (SKG) during pre-swing, finding increased abduction despite improved knee flexion and toe clearance. Thus, our hypothesis was that hip abduction is not a compensation for reduced knee flexion. We simulated the kinematics of post-stroke SKG on unimpaired individuals with three factors: a knee orthosis to reduce knee flexion, an ankle-foot orthosis commonly worn by those post-stroke, and matching gait speeds. We compared spatiotemporal measures and kinematics between experimental factors within healthy controls and with a previously recorded cohort of people with post-stroke SKG. We focused on frontal plane motions of hip and pelvis as possible compensatory mechanisms. We observed that regardless of gait speed, knee flexion restriction increased pelvic obliquity (2.8°, p < 0.01) compared to unrestricted walking (1.5°, p < 0.01), but similar to post-stroke SKG (3.4°). However, those with post-stroke SKG had greater hip abduction (8.2°) compared to unimpaired individuals with restricted knee flexion (4.2°, p < 0.05). These results show that pelvic obliquity, not hip abduction, compensates for reduced knee flexion angle. Thus, other factors, possibly neural, facilitate exaggerated hip abduction observed in post-stroke SKG.     

Natural neuroprotective alkaloids from Stephania japonica (Thunb.) Miers

Modulating inflammatory responses after stroke can prevent brain injury and, therefore, improve neurological outcome. Stephania japonica (Thunb.) Miers is a Chinese folk medicine with the function of dispelling the “wind and blockage” in the human body according to the Chinese medicine theory, in which the symptoms of stroke are caused by the “wind and blockage” in the body. In this paper, we for the first time linked S. japonica to stroke by clarifying fifteen alkaloidal constituents including five undescribed (1–5) ones and screening out six hasubanan type alkaloids (1–4, 7, 15) that elicited stronger anti-neuroinflammatory activities than the positive drug. Moreover, the total alkaloid fraction (ASJ) with previously undescribed 3 as the main component was subject to the in vivo evaluation of the protective effect in the MCAO-induced brain injury. The results showed that ASJ exhibited potent protective effect against brain injury in the MCAO rat model. The results reported in this paper suggested that the hasubanan alkaloids from S. japonica would be an important molecular source for discovering novel therapeutic agents for neuroinflammation-related diseases, such as stroke diseases.