Integrins such as αvβ3, α5β1 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke can promote angiogenesis, which in turn improves functional recovery. In addition, the integrin αvβ3 inhibitor can block the blood-brain barrier (BBB) leakage induced by vascular endothelial growth factor (VEGF) and also can reduce inflammatory reaction, decrease the deposition of fibrinogen. Other studies showed that integrin αvβ3 is not essential in revascularization. Therefore, the effect of integrin αvβ3 in the whole process of brain function recovery merits further study.
Animals ; Blood Vessels ; drug effects ; physiopathology ; Blood-Brain Barrier ; drug effects ; metabolism ; physiopathology ; Humans ; Integrin alphaVbeta3 ; antagonists & inhibitors ; metabolism ; Integrins ; metabolism ; Models, Biological ; Peptides, Cyclic ; pharmacology ; Stroke ; metabolism ; physiopathology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo evaluate the application value of percutaneous endoscopic gastrostomy (PEG) for home nutrition support in patients with stroke and post-traumatic brain.

METHODSWe retrospectively analyzed the clinical data of the 16 patients with stroke and post-traumatic brain, including cerebral infarction (n = 9), cerebral hemorrhage ( n = 5), subarachnoid hemorrhage (n = 1), and cerebral trauma (n = 1). All these patients underwent PEG in our hospital because they were not able to be orally fed.

RESULTSThe weight, triceps skinfold thickness, mid-upper arm muscle circumference, and serum albumin, hemoglobin, and lympholeukocyte cell counts 30, 60, and 120 days after hospital discharge were significantly higher than those at hospital discharge (P <0.05 or P <0.01). The NIHSS scores 30, 60, and 120 days after hospital discharge were 14.0 +/- 1.3, 14.0 +/- 1.1, and 3.0 +/- 1.2, respectively, which were significantly lower than 16.0 +/- 1.2 at hospital discharge (all P <0.05). Complications included gastric contents retention (n = 1), backstreaming (n = 1), aspirated pneumonia (n = 1), and intra-cushion syndrome (n = 1).

CONCLUSIONSPEG for home nutrition support is useful for the treatment of patients with stroke and post-traumatic brain with dysphagia and malnutrition after long-term coma. It can help to avoid the deterioration of nutritional status and improve the quality of life.

Adult ; Aged ; Aged, 80 and over ; Cerebral Hemorrhage ; physiopathology ; Cerebral Infarction ; physiopathology ; Enteral Nutrition ; methods ; Female ; Gastroscopy ; adverse effects ; methods ; Gastrostomy ; adverse effects ; methods ; Hemoglobins ; metabolism ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Serum Albumin ; metabolism ; Stroke ; physiopathology ; Subarachnoid Hemorrhage ; physiopathology

Heart failure with preserved ejection fraction (HFPEF) is a global health problem of considerable socioeconomic burden. It is projected to worsen with the aging population worldwide. The lack of effective therapies underscores our incomplete understanding of this complex heterogeneous syndrome. A novel paradigm has recently emerged, in which central roles are ascribed to systemic inflammation and generalized endothelial dysfunction in the pathophysiology of HFPEF. In this review, we discuss the role of the endothelium in cardiovascular homeostasis and how deranged endothelial-related signaling pathways contribute to the development of HFPEF. We also review the novel therapies in various stages of research and development that target different components of this signaling pathway.
Animals ; Endothelium, Vascular/*physiopathology ; Heart Failure/diagnosis/metabolism/*physiopathology/therapy ; Humans ; Inflammation/diagnosis/metabolism/*physiopathology/therapy ; Inflammation Mediators/metabolism ; Prognosis ; Risk Factors ; Signal Transduction ; *Stroke Volume ; *Ventricular Function, Left

Depression is an important post-stroke sequela with negative impact on mortality, functional outcome and quality of life. Changes in cytokines have been hypothesized to be associated with the etiology of post-stroke depression (PSD). The altere dhypothalamic-pituitary-adrenal (HPA) functioning is associated with the onset of depression. The activity of HPA could induce the fluctuations of cortisol levels. In this study, we prospectively checked interleukin 6 (IL-6) and cortisol levels in patients with early ischemic stroke. It was hypothesized that early serum IL-6 and cortisol fluctuations in stroke patients were the predictions of PSD. Totally, 100 participants were selected from stroke inpatients consecutively admitted to the Department of Neurology, Tongji Hospital from July 2014 to December 2015. Fifty health people served as the controls. The serum of all the patients was collected at 8:00 am and 4:00 pm respectively one week after stroke. The serum of controls was collected only at 8:00 am. The levels of IL-6 were analyzed by enzyme-linked immunosorbent assay kit, and those of cortisol were detected by chemiluminescence immunoassay. On the 3rd week after stroke, the patients were enrolled to the PSD group and non-PSD group based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and The Hamilton Depression Rating Scale (HAMD-21, score>7). The IL-6 level (13.24±2.89 ng/L) was elevated significantly in PSD groups as compared with that in non-PSD group and control group respectively (P<0.05 for both), but there was no significant difference in the IL-6 level between non-PSD group and control group. The patients in both PSD group and non-PSD group had significantly elevated morning cortisol levels in comparison with those in the control group (P<0.05; for PSD, non-PSD and control: 508.86±119.51, 420.83±70.04 and 340.40±76.30 nmol/L respectively). Moreover, afternoon cortisol levels in PSD group were significantly higher than those in non-PSD group, and the morning baseline cortisol levels in these two groups were similar (P>0.05). It was suggested that PSD generally runs a chronic course and is related to a variety of adverse health outcomes including increased disability, morbidity and mortality. This study will help the screening of potential PSD in the early stage.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Depression ; blood ; etiology ; physiopathology ; Female ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; metabolism ; Interleukin-6 ; blood ; Male ; Middle Aged ; Stroke ; blood ; complications ; physiopathology

OBJECTIVETo investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients.

METHODSFifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores.

RESULTSNo significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P<0.05). On d14 after admission hs-CRP (13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P<0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P<0.05).

CONCLUSIONNutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.

C-Reactive Protein ; metabolism ; Complement C3 ; metabolism ; Humans ; Hydrocortisone ; blood ; Nutritional Status ; Prealbumin ; metabolism ; Prognosis ; Severity of Illness Index ; Stroke ; diagnosis ; physiopathology

OBJECTIVETo explore the correlation of lymphocyte G protein-coupled receptor kinases 2 (GRK2) expression of the very elderly with chronic heart failure (HF) and heart ejection fraction (EF).

METHODS16 elderly patients with chronic heart failure were divided into 2 groups as following: EF < 45% (n=7), EF > or = 45% (n=9); and health elderly as control (n=8). Lymphocytes were obtained from blood, reverse transcription polymerase chain reaction were used to measure GRK2 mRNA levels.

RESULTSLymphocyte GRK2 mRNA levels of EF < 45% group were higher than that of EF > 45% group, which were greater than that of control.

CONCLUSIONElevation of lymphocyte GRK2 levels in HF is associated with heart EF, lymphocytes may provide a surrogate for monitoring cardiac GRK2 in human HF.

Aged, 80 and over ; Chronic Disease ; G-Protein-Coupled Receptor Kinase 2 ; genetics ; metabolism ; Heart Failure ; blood ; physiopathology ; Humans ; Lymphocytes ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Stroke Volume ; physiology

The aim of this study was to evaluate the effect of early motor balance and coordination training on functional recovery and brain plasticity in an ischemic rat stroke model, compared with simple locomotor exercise. Adult male Sprague-Dawley rats with cortical infarcts were trained under one of four conditions: nontrained control, treadmill training, motor training on the Rota-rod, or both Rota-rod and treadmill training. All types of training were performed from post-operation day 1 to 14. Neurological and behavioral performance was evaluated by Menzies' scale, the prehensile test, and the limb placement test, at post-operation day 1, 7, and 14. Both Rota-rod and treadmill training increased the expression of synaptophysin in subcortical regions of the ischemic hemisphere including the hippocampus, dentate gyrus, and thalamus, but did not affect levels of brain-derived neurotrophic factor or tyrosin kinase receptor B. The Rota-rod training also improved Menzies' scale and limb placement test scores, whereas the simple treadmill training did neither. The control group showed significant change only in Menzies' scale score. This study suggests that early motor balance and coordination training may induce plastic changes in subcortical regions of the ischemic hemisphere after stroke accompanied with the recovery of sensorimotor performance.
Animals ; Brain Ischemia/metabolism/physiopathology ; Brain-Derived Neurotrophic Factor/metabolism ; Dentate Gyrus/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Immunohistochemistry ; Male ; Motor Activity ; Neuronal Plasticity/physiology ; Physical Conditioning, Animal ; Physical Therapy Modalities ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism ; Stroke/*metabolism/physiopathology ; Synaptophysin/*metabolism ; Thalamus/metabolism ; Time Factors

The incidence of diastolic heart failure increases dramatically with age. We investigated the impact of long-term exercise training on age-related diastolic dysfunction. Old (25-month-old) male Fischer 344 rats were studied after 12 weeks of treadmill exercise training or sedentary cage life (N=7, in each group). We determined cardiac performance using a pressure-volume conductance catheter and magnetic resonance imaging. Collagen volume fraction (CVF) and myocardial collagen solubility by pepsin as an index of advanced glycation end products (AGEs) crosslinked collagen were measured. The maximal slope of systolic pressure increment (+dP/dt) and the slope of end-systolic pressure-volume relation were higher, and end diastolic volume (EDV), delta EDV (the percentage of the EDV increment-to-baseline EDV) and the slope of end-diastolic pressure-volume relation were lower in training group. The maximal slope of diastolic pressure decrement (-dP/dt) and time constant of LV pressure decay (tau) had no difference. AGEs cross-linked collagen, not CVF was reduced by exercise training. Long-term exercise training appears to attenuate age-related deterioration in cardiac systolic function and myocardial stiffness and could be reduce in pathologic AGEs cross-linked collagen in myocardium.
*Aging ; Animals ; Blood Pressure ; Collagen/*metabolism ; Glycosylation End Products, Advanced/metabolism ; Heart Failure, Diastolic/metabolism/*physiopathology ; Magnetic Resonance Imaging ; Male ; Myocardium/*metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Inbred F344 ; Solubility ; Stroke Volume/physiology

The present study is to assess the prophylactic effect of quinacrine (QA) , an anti-malarial drug, against heatstroke in rats. Conscious rats were orally given equal volume normal saline or QA (dissolved in normal saline and final dosage for rats was 4.5, 9.0 and 18 mg x kg(-1)). An hour later rats were put into a warm water circulated hot chamber (41.0 +/- 0.5) degrees C. Rectal temperature (core temperature, T(co)) of rats in hot chamber was continuously monitored by a thermocouple. T(co) and survival time of rats showed that QA pre-treatment postponed the hyperthermia, and increased the survival time of rats in hot chamber. Primary striatum neurons' culture from new born rats was maintained with D-MEM and 10% FBS. After immuno-cytochemistry identification with antibodies against neural specific proteins, culture received 20 micromol x L(-1) QA only for 1 h and followed by 43.0 degrees C heat treatment for another hour, or 20 micromol x L(-1) QA for 1 h followed by 43.0 degrees C heat treatment for another hour. Control culture received heat treatment only. Cultures were labeled with the fluorescent indicator DPH and the relative membrane fluidity of neurons was measured with the help of fluorescent polarized spectrophotometer. [3H] Arachidonic acid (AA) labeled membrane of E. Coli cells was used as substrate to determine cPLA2 activity of neurons. Gas chromatography and mass spectrum were also employed to detect on the level of fatty acids level in rat striatum neurons. Results from cells indicated that inhibition of cPLA2, reduction the release of active fatty acids such as AA, and possibly, stabilization of the cell membrane which was disturbed by hot treatment, may contribute to the mechanism underlying heat protection and heatstroke preventive effects of quinacrine.
Animals ; Cells, Cultured ; Corpus Striatum ; drug effects ; pathology ; Fatty Acids ; metabolism ; Heat Stroke ; metabolism ; physiopathology ; prevention & control ; Hot Temperature ; adverse effects ; Male ; Membrane Fluidity ; drug effects ; Neurons ; enzymology ; metabolism ; physiology ; Phospholipases A2 ; metabolism ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar

Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.
Animals ; Axons/pathology ; Cerebral Cortex/physiology ; Disease Models, Animal ; Electric Stimulation ; Motor Activity/physiology ; Rats ; Rats, Sprague-Dawley ; Stroke/metabolism/*pathology/physiopathology