Effects of acupuncture on declined cerebral blood flow,impaired mitochondrial respiratory function and oxidative stress in multi-infarct dementia rats

Brain energy disorders and oxidative stress due to chronic hypoperfusion were considered to be the major risk factors in the pathogenesis of dementia. In previous studies, we have demonstrated that acupuncture treatment improved cognitive function of VaD patients and multi-infarct dementia (MID) rats. Acupuncture therapy also increased the activities of glycometabolic enzymes in the brain. But it is not clear whether acupuncture treatment compensates neuronal energy deficit after cerebral ischemic through enhancing the activities of glucose metabolic enzymes and preserving mitochondrial function, and whether acupuncture neuroprotective effect is associated with activations of mitochondrial antioxidative defense system. So, the effect of acupuncture therapy on cognitive function, cerebral blood flow (CBF), mitochondrial respiratory function and oxidative stress in the brain of MID rats was investigated in this study. The results showed that acupuncture treatment significantly improved cognitive abilities and increased regional CBF of MID rats. Acupuncture elevated the activities of total SOD, CuZnSOD and MnSOD, decreased the level of malondialdehyde (MDA) and superoxide anion, regulated the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) in mitochondria, and raised the level of the respiratory control index (RCI) and P/O ratio and the activities of mitochondrial respiratory enzymes of MID rats. These results indicated that acupuncture treatment improved cognitive function of MID rats; and this improvement might be due to increased CBF, which ameliorated mitochondrial dysfunction induced by ischemia and endogenous oxidative stress system of brain.     

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.     

Brain μ-Calpain Autolysis During Global Cerebral Ischemia

Abstract: Proteolytic degradation of numerous calpain substrates, including cytoskeletal and regulatory proteins, has been observed during brain ischemia and reperfusion. In addition, calpain inhibitors have been shown to decrease degradation of these proteins and decrease postischemic neuronal death. Although these observations support the inference of a role for μ-calpain in the pathophysiology of ischemic neuronal injury, the evidence is indirect. A direct indicator of μ-calpain proteolytic activity is autolysis of its 80-kDa catalytic subunit, and therefore we examined the μ-calpain catalytic subunit for evidence of autolysis during cerebral ischemia. Rabbit brain homogenates obtained after 0, 5, 10, and 20 min of cardiac arrest were electrophoresed and immunoblotted with a monoclonal antibody specific to the μ-calpain catalytic subunit. In nonischemic brain homogenates the antibody identified an 80-kDa band, which migrated identically with purified μ-calpain, and faint 78- and 76-kDa bands, which represent autolyzed forms of the 80-kDa subunit. The average density of the 80-kDa band decreased by 25 ± 4 ( p = 0.008) and 28 ± 9% ( p = 0.004) after 10 and 20 min of cardiac arrest, respectively, whereas the average density of the 78-kDa band increased by 111 ± 50% ( p = 0.02) after 20 min of cardiac arrest. No significant change in the density of the 76-kDa band was detected. These results provide direct evidence for autolysis of brain μ-calpain during cerebral ischemia. Further work is needed to characterize the extent, duration, and localization of μ-calpain activity during brain ischemia and reperfusion as well as its role in the causal pathway of postischemic neuronal injury.     

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.     

Molecular Characteristics and Peptide Specificity of Vasoactive Intestinal Peptide Receptors from Rat Cerebral Cortex

Vasoactive intestinal peptide (VIP) receptors have been identified in CNS by their chemical specificity and molecular size. Using synaptosomes isolated from rat cerebral cortex, it was shown that central VIP receptors discriminated among natural and synthetic VIP-related peptides, because half-maximal inhibition of [125I]VIP binding to synaptosomes was obtained for 0.6 nM VIP, 9 nM peptide histidine isoleucineamide (PHI), 50 nM VIP 2-28, 70 nM secretin, 100 nM rat growth hormone-releasing factor (GRF), and 350 nM human GRF. Other peptides of the VIP family, such as glucagon and gastric inhibitory polypeptide, did not interact with cortical VIP receptors. The molecular components of VIP receptors in rat cerebral cortex were identified after [125I]VIP cross-linking to synaptosomes using the cross-linker dithiobis(succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of synaptosomal proteins revealed two major [125I]VIP-protein complexes of Mr 49,000 and 18,000. The labeling of the Mr 49,000 component was specific, because it was abolished by native VIP, whereas the labeling of the Mr 18,000 component was not. Natural VIP agonists reduced the labeling of the Mr 49,000 component with the following order of potency: VIP greater than PHI greater than secretin approximately equal to rat GRF. In contrast, glucagon and octapeptide of cholecystokinin were without effect, a result indicating its peptide specificity. Densitometric scanning of autoradiographs showed that the labeling of the Mr 49,000 component was inhibited by low VIP concentrations between 10(-10) and 10(-6) M (IC50 = 0.8 nM), a result indicating the component's high affinity for VIP.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effects of N-Acetyl Aspartate, Aspartate, and Glutamate on cAMP and cGMP Levels in Developing Rat Cerebral Cortex

N-Acetyl-aspartate (N-Ac-Asp) incubated with minced cerebral cortex caused a dose-dependent increase in the levels of cAMP and cGMP. This effect was followed during postnatal development. N-Ac-Asp elicits the greatest increase in cAMP in 5-day-old and in cGMP in 40-day-old rats. The levels of cyclic AMP were always higher than those of cGMP. We also studied the effects of L-aspartate (Asp) and L-glutamate (Glu) on the levels of cyclic nucleotides in the cerebral cortex minces of rats different ages, and observed that both amino acids produced the maximum increase in cAMP at 10 days, whereas in the case of cGMP the maximal effect of Asp occurs earlier than 20 days and of Glu after 40 days. In the adult rat, the N-Ac-Asp effect on cAMP was greater than that produced by either Asp or Glu, whereas the levels of cGMP were similarly affected by all three. The data show a peak response of cAMP and cGMP to N-Ac-Asp, Asp, and Glu during cortical maturation. Because this response varies with postnatal time, N-Ac-Asp, and Glu may act upon different receptor sites.     

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.