Evaluation of ghrelin,nesfatin-1 and irisin levels of serum and brain after acute or chronic pentylenetetrazole administrations in rats using sodium valproate

ABSTRACT

Objectives: In this study, we aim to reveal the alterations (due to seizure) in the serum and brain levels of nesfatin-1, ghrelin and irisin after acute or chronic pentylenetetrazole administrations in rats using sodium valproate.

Methods: 35 Wistar albino rats were randomly divided into five groups: Control, Acute Pentylenetetrazole group (APTZ), Acute Pentylenetetrazole+ Valproate group (AVPA), PTZ kindling group (PTZk) and PTZ kindling+ Valproate group (KVPA). Serum and brain levels of ghrelin, nesfatin-1 and FNDC5/irisin were determined with ELISA.

Results: Serum levels of ghrelin were significantly decreased in APTZ and PTZk groups compared to the control (p < 0.01). There was a statistically significant decrease in brain levels of ghrelin in all groups compared to the control group (p < 0.01). There was a statistically significant increase in serum nesfatin-1 levels in the APTZ and PTZk groups compared to the control (p < 0.05). Serum levels of nesfatin-1 were similar to the control group in both the acute and the chronic treatment groups. There was a statistically significant increase in brain nesfatin-1 levels of the KVPA group compared to the control (p < 0.05). Serum and brain levels of FNDC5/irisin were found significantly increased in APTZ, AVPA and PTZk groups compared to the control (p < 0.01).

Conclusions: Statistically significant alterations were detected in the serum and brain levels of these three peptides in both the PTZ-induced chronic epilepsy model and acute seizure model. The results of this study may suggest that the increase in FNDC5/irisin and nesfatin-1 levels, and the decrease in ghrelin levels may contribute to seizure pathophysiology. However, further studies are needed in order to confirm our hypothesis.     

Mapping of Cerebral Metabolic Activation in Three Models of Cholinergic Convulsions

Glucose utilization of four cerebral cortex and 35 subcortical regions (CGU) was analyzed in three models of cholinergic seizures induced by the following compounds: 1) soman (pinacolylmethylphosphonofluoridate) an organophosphorus cholinesterase inhibitor, 100 μg/kg SC after pretreatment with pyridostigmine 26 μg/kg IM (n = 6); 2) physostigmine, a carbamate cholinesterase inhibitor, 1.31 mg/kg infused IV over 75 min (n = 6); and 3) pilocarpine, a direct cholinergic agonist, 30 mg/kg SC (n = 6). Physostigmine and pilocarpine were preceded by 3 mmol/kg LiCl IP 20 hrs earlier. Animals injected with saline SC (n = 6) were used as controls. Step-wise discriminant analysis successfully classified 100% of the cases into the four experimental groups with data from only six regions. Pyridostigmine-soman induced the most widespread and greatest increases in CGU. More restricted and lower levels of activation were observed with Li-pilocarpine while Li-physostigmine induced significant increases in CGU only in globus pallidus, entopeduncular nucleus, and substantia nigra. These three regions, which are functionally related, were also activated in the other two models of cholinergic convulsions and may represent the initial step in cholinergic activation of the CNS. Li-pilocarpine failed to activate most of the brainstem and the superior colliculus. All cortical regions were activated by Li-pilocarpine and pyridostigmine-soman, while they were inhibited by Li-physostigmine. This phenomenon may be due in part to the lack of activation with physostigmine of the basal forebrain nuclei (lateral septum, medial septum, vertical and horizontal limbs of the diagonal band, and substantia innominata) resulting in a decreased drive of cortical metabolism.     

Association of BDNF G196A Gene Polymorphism with Ischemic Stroke Occurrence and its 6-Month Outcome in an Iranian Population

Background: Genetic factors like the allele for Brain-Derived Neurotrophic Factor (BDNF) are associated with the outcome of ischemic stroke most likely through affecting neural differentiation and synaptic plasticity. Studies of the association of BDNF G196A gene polymorphism and long-term ischemic stroke outcome in various populations have not been concordant.

Objective: In this research, the association of BDNF G196A gene polymorphism and ischemic stroke occurrence were studied in a northern Iranian population with a glance to its 6-month outcome.

Methods: The genetic variant of BDNF G196A was examined in Ischemic Stroke (IS) patients (n = 206) and control group (n = 200). In IS individuals, outcome variables such as stroke severity, functional disability, and cognitive impairment were examined, respectively, by NIHSS, Barthel Index, and MoCA in an average of 202 days after the stroke occurrence.

Results: The frequency of risk allele G was 12.1% in IS patients and 5.5% in healthy individuals; and the difference was statistically significant (p < 0.0001). The frequency of risk genotype GG, heterozygote and homozygote were 0% and 1%, 24%.3% and 9%, 75.7% and 90%, respectively, for IS and control groups (p < 0.05). After controlling the phenotype confounding factors, logistic regression analysis showed that there was a borderline significant relationship between genotype BDNF GA + GG and IS occurrence (AOR = 1.997,95% CI: 0.252–1.010, p = 0.051). There was no significant difference between the various genotypic groups regarding the severity of the stroke and functional disability. Yet, G allele carriers had more cognitive impairment after IS (p = 0.002).

Conclusion: For the first time in an Iranian population, it was demonstrated that BDNF G196A variant plays a major role in stroke occurrence and consequences. It is suggested that, after IS, G allele carriers should have precedence for medicinal and rehabilitation interventions, in order to reduce their cognitive deficiency.     

Intraperitoneal cannabidiol attenuates neonatal germinal matrix hemorrhage-induced neuroinflamation and perilesional apoptosis

ABSTRACT

Background. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage.

Methods. 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted.

Results. Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the Stratum oriens of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol.

Conclusion. The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.     

Paracellular tightness and the functional expression of efflux transporters P-gp and BCRP in bEnd3 cells

Objective The blood–brain barrier (BBB), regulating brain homeostasis and limiting the entry of most drugs, is characterized by intercellular tight junctions and the presence of transporters. In this study, the paracellular tightness and functional expression of efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) were evaluated in mouse brain immortalized cell line bEnd3 to prove it as a useful BBB-mimicking system for biological and pharmacological research.

Methods The presence of P-gp, BCRP and tight junction proteins occludin, claudin-5 and ZO-1 were validated by RT-PCR and Western blot. The tightness of bEnd3 monolayers was evaluated by measuring the permeability of hydrophilic marker Lucifer yellow. The P-gp functionality was identified by intracellular uptake assay using Rhodamine 123 (R123) as P-gp substrate and verapamil as P-gp inhibitor. The BCRP functionality was identified by flow cytometric analysis of mitoxantrone accumulation and fluorescence microscopic analysis of Hoechst 33342 accumulation using Ko-143 as BCRP inhibitor.

Results The bEnd3 cells demonstrated the expression of P-gp, BCRP and tight junction proteins occludin, claudin-5 and ZO-1 at mRNA and protein levels. The permeability coefficient of Lucifer yellow was 1.3 ± 0.13 × 10^?3 cm/min, indicating the moderate paracellular tightness barrier formed by bEnd3 cells. The verapamil induced a higher cellular uptake of Rhodamine 123, and Ko-143 significantly elevated cellular accumulation of mitoxantrone and Hoechst 33342, suggesting the P-gp and BCRP functionality shown by bEnd3 cells.

Conclusions The bEnd3 cell line represents a useful in vitro tool for studying BBB characteristics and drug transport mechanisms at the BBB.     

Psychocardiological disorder and brain serotonin after comorbid myocardial infarction and depression: an experimental study

Objectives We investigated whether trimetazidine pretreatment can regulate central and peripheral serotonin (5-HT) in rats of myocardial infarction (MI) combined with depression.

Methods Forty rats were randomly assigned to a sham operation group (n = 10) and a disease model group (n = 30). The sham operation group was pretreated with normal saline for 4 weeks. The disease model group was randomly assigned further into a negative control subgroup, a positive control subgroup, and a treatment subgroup — the groups received saline, sertraline, and trimetazidine pretreatment, respectively, for 4 weeks, then the rats were subjected to MI combined with depression. 5-HT concentrations in the serum, platelet lysate, and cerebral cortex lysate were analyzed with ELISA.

Results The levels of serum 5-HT and platelet 5-HT were significantly lower in negative control subgroup than the sham operation group (P < 0.05), but there was no significant difference in brain 5-HT (P > 0.05). Compared with the negative control subgroup, the levels of serum 5-HT and platelet 5-HT in the positive control subgroup and treatment subgroup were significantly higher (P < 0.05). The levels of 5-HT in brain of the positive control subgroup and treatment subgroup were significantly lower than those in the negative control subgroup (P < 0.05).

Conclusions Trimetazidine pretreatment can increase serum and platelet 5-HT levels in rats with MI and depression and decrease 5-HT levels in brain tissue. This regulatory effect on central and peripheral 5-HT suggests a role for trimetazidine in the treatment of psychocardiological diseases.     

Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K/Akt signaling pathway

Objective: Neuronal autophagy and apoptosis play an irreplaceable role in brain injury pathogenesis and may represent a hopeful target for treatment. Previous studies have demonstrated that administration of quercetin-attenuated brain damage in a variety of brain injury models including traumatic brain injury (TBI). However, whether PI3K/Akt signaling pathway mediates the neuroprotection of quercetin following TBI is not well clarified. We sought to propose a hypothesis that quercetin could attenuate neuronal autophagy and apoptosis via enhancing PI3K/Akt signaling.

Methods: All rats were randomly arranged into four groups as follows: sham group (n = 25), TBI group (n = 25), TBI + quercetin group (n = 25), TBI + quercetin + LY294002 group (n = 25). Quercetin (Sigma, USA, dissolved in 0.9% saline solution) was administered intraperitoneally at a dose of 50 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and spatial cognitive function was assessed by the neurologic severity score and Morris water maze, respectively. Immunohistochemistry staining and western blotting was used to evaluate the expression of LC3, p-Akt, caspase-3, Bcl-2, and Bax.

Results: Quercetin treatment significantly attenuated TBI-induced neurological impairment (1–3 days, p < 0.05) and improved cognitive function (5–8 days, p < 0.05). Double immunolabeling demonstrated that quercetin significantly reduced the LC3-positive cells co-labeled with NeuN, whereas significantly enhanced p-Akt-positive cells co-labeled with NeuN. Furthermore, quercetin treatment reduced the expression of LC3、caspase-3 and Bax levels induced following TBI (p < 0.05), and increased the expression of p-Akt and Bcl-2 at 48 h (p < 0.05).

Conclusion: In conclusion, our observations indicate that post-injury treatment with quercetin could inhibit neuronal autophagy and apoptosis in the hippocampus in a rat model of TBI. The neuroprotective effects of quercetin may be related to modulation of PI3K/Akt signaling pathway.     

Morphine reduces mouse microglial engulfment induced by lipopolysaccharide and interferon-γ via δ opioid receptor and p38 mitogen-activated protein kinase

Objective To investigate the effects of morphine on microglial phagocytosis during neuroinflammation.

Methods C8-B4 mouse microglial cells were exposed to various concentrations of morphine after the stimulation with lipopolysaccharide and interferon-γ and then fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia. Naloxone, β funaltrexamine, or naltrindole was used with 1 μM morphine to assess the involvement of specific opioid receptor. P38 and phosphorylated p38 were determined by Western blotting. A p38 mitogen-activated protein kinase (MAPK) activator (anisomycin 0.1 μM) or inhibitor (SB 203580, 20 μM) was used to determine the involvement of p38 MAPK pathway.

Results Morphine decreased lipopolysaccharide and interferon-γ-induced microglial engulfment except the highest concentration (10 μM) and both naloxone and naltrindole (a selective δ opioid receptor antagonist) attenuated morphine effect (p < 0.001). The phosphorylated p38 was up-regulated in lipopolysaccharide and interferon-γ group compared with control group (p < 0.001). This up-regulation was decreased by 1 μM morphine (p < 0.001). However, naltrindole abolished this morphine effect (p = 0.015). SB203580 blocked the increased microglial engulfment induced by lipopolysaccharide and interferon-γ (p < 0.001); whereas, anisomycin enhanced the morphine-induced decrease of engulfment (p < 0.001).

Conclusion Morphine reduced mouse microglial engulfment induced by lipopolysaccharide and interferon-γ. This morphine effect seems to be mediated by δ opioid receptor and via p38 MAPK inhibition.     

Increased serum midkine levels in autism spectrum disorder patients

Background: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis.

Methods: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale.

Results: Our data showed that the serum MK concentration in ASD patients (mean ± SD, 11.51 ± 8.53 pg/ml) is significantly higher than healthy controls (mean ± SD, 6.19 ± 3.94 pg/ml) (p = 0.007).

Conclusions: According to these results, MK may play a role in ASD pathogenesis.     

An examination of changes in spoken productions within constraint-induced aphasia therapy

Background: Researchers are continuing to investigate the impact of constraint-induced aphasia therapy (CIAT) programs on the spoken language capabilities of people with aphasia at the utterance and discourse level. Currently, there is a lack of consensus on how spoken productions should be measured and there are no investigations that explore the spoken language that people with aphasia use during a CIAT program. Therefore, clinicians and researchers cannot truly know if they are utilizing the most revealing outcome measures to illuminate treatment induced gains in spoken production.

Aims: The purpose of this investigation was to examine the within treatment learning of people with aphasia in a CIAT program, by exploring the sensitivity of measures of content, length, syntax, and efficiency at the utterance level and reveal linguistic gains.

Methods & Procedures: A repeated measures design was employed to examine 200 utterance samples from eight participants with various types and severity of chronic aphasia between early and late treatment sessions. The measures of correct information units (CIUs), counted words, T-Units, CIUs per utterance, mazes, and mean length of utterance were compared.

Outcomes & Results: Nonparametric analyses revealed significant positive gains for the participants in the number of produced CIUs (p = 0.035), counted words (p = 0.012), T-Units, (p = 0.025), and CIUs per utterance (p = 0.012). A significant decrease in the amount of mazes (p = 0.028) was also found. No significant increase was detected in the participants’ mean length of utterance (p = 0.161).

Conclusions: The participants displayed advances in the content, syntax, and efficiency of their spoken utterances during the course of a 10-day CIAT program. Specifically, the measures of CIUs, counted words, mazes, and CIUs per utterance emerged as being the most sensitive to capture the within treatment changes made by the participants. The utility of these measures should be further explored to establish treatment baselines, demonstrate within treatment learning, and show posttreatment gains.     

Topical application of the hematostatic agent Surgiflo® could attenuate brain injury in experimental TBI mice

Object: The pathologies resulting from traumatic brain injury (TBI) have been thoroughly studied, but rarely have the effects of bleeding and coagulation in the early stage of TBI been considered. In this study, we investigated the effects of topical Surgiflo^® application on brain injury in experimental TBI mice using S100β, MAP-2 and mNSS scores.

Methods: TBI was induced by modified weight drop injury in male C57BL/6 mice. The mice were then randomly divided into (i) the sham group, (ii) TBI mice applied with saline (vehicle), and (iii) TBI mice applied with Surgiflo^® in the same volume. Modified neurological severity scores (mNSS) were measured on days 0 (before surgery), 1, 3, 7, and 28 to evaluate neurologic functional deficits. At day 28, the mice were sacrificed, and the forebrains were sliced. The effects of Surgiflo^® on microtubule-associated protein 2 and serum S100β protein were examined by immunohistochemistry and electro-chemiluminescence immunoassay.

Results: Serum S100β protein levels were significantly elevated at different time points (24 h, 3 days, 7 days) in the TBI groups (p < 0.01) compared to normal control groups. Surgiflo^® induced a lower concentration of serum S100β protein levels at day 3 (p < 0.05) and day 7 (p < 0.05) compared to the TBI group applied with saline. H&E staining showed that Surgiflo^® treatment led to a 45% decrease in cortical brain lesion volume and in subcortical white matter 28 days after TBI. Compared with the saline-treated group, the number of MAP2-positive cells was significantly increased in the perilesional area of the Surgiflo^®-treated group. The Surgiflo^®-treated group exhibited lower mNSS scores on days 7 and 28 than did the saline-treated group.

Discussion: Surgiflo^® treatment produced a significant decrease in serum S100β protein levels in TBI mouse models, which may lead to an improvement in the recovery of TBI models.     

Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats

Objectives: In this study, we aimed to evaluate the effect of the Ischemic preconditioning (IPreC) on the expression profile of cerebral miRNAs against stroke by induced transient middle cerebral artery occlusion (MCAo) in diabetic rats.

Methods: Eighty male Spraque Dawley rats were allocated to eight groups. In order to evaluate the expression profile of miRNAs, we induced transient MCAo seven days after STZ-induced diabetes (DM). Also we performed IPreC 72 h before transient MCAo to assess whether IPreC could have a neuroprotective effect against ischemia-reperfusion injury.

Results: The general characteristics of STZ-treated rats included reduced body weight and elevated blood glucose levels compared to non-diabetic ones. We demonstrated that miRNA expression profiles, which are determined for biological functions such as aquaporin 4 formation (miR-29b-2, miR-124a-3p, miR-130a, miR-223 and miR-320a), glutamate toxicity (miR107, miR-145, miR-223), salvageable ischemic area (miR-9a, miR-19b, miR-29b-2, miR-341, miR-339–5p, miR-15–5p, miR-99b-5p), and neoangiogenesis (let-7f-5p, miR-126a and miR-322–3p), were regulated following IPreC. Ischemic preconditioning before cerebral ischemia significantly reduced infarction size compared with the other groups [IPreC + MCAo (27 ± 11 mm³) vs. MCAo (109 ± 15 mm³) p < 0.001; DM + IPreC + MCAo (38 ± 9 mm³) vs. DM + MCAo (165 ± 41 mm³) p < 0.001, respectively].

Discussion: The study results revealed the neuroprotective effects of ischemic preconditioning, supported with the upregulated pro-survival miRNAs in MCA infarcts.     

The effect of orexin-A on motor and cognitive functions in a rat model of Parkinson’s disease

Objective: The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson’s disease. Methods: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests. Cognitive function was assessed by passive avoidance test (Shuttle box). Results: OX-A administration in 6-OHDA treated rats remarkably increased the time which animals run on rod (in rotarod test) and also the latency to fall (in hanging test) (P < 0.01 and P < 0.001, respectively). Conversely, administration of SB in 6-OHDA-treated rats decreased the mentioned indices (P < 0.05 for latency to fall). Administration of agonist and/or antagonist of orexin-1 receptors had no significant effect on 6-OHDA induced cognitive impairment in rats. Conclusion: Results of this study suggest that the orexinergic system might be involved in sensory-motor deficits of Parkinson’s disease.     

Low free triiodothyronine levels are related to symptomatic intracranial hemorrhage and poor functional outcomes after intravenous thrombolysis in acute ischemic stroke patients

Background and Objective: Low free triiodothyronine (fT3) levels have been associated with increased mortality and poor functional outcomes in patients with stroke. However, the research of relationship between fT3 levels and acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT) is scarce. We aimed to investigate the association of fT3 levels with symptomatic intracranial hemorrhage (sICH) and functional outcomes at discharge in AIS patients with IVT.

Methods: Patients with AIS admitted to West China hospital, Sichuan University, who had underwent IVT treatment, were consecutively and retrospectively included. Demographic and clinical information were collected and analyzed according to the levels of fT3. We used logistic regression analysis to estimate the multivariable adjusted association of fT3 levels and post-IVT sICH, and functional outcomes at discharge.

Results: Among the 46 patients (26 males; mean age, 63.6 years) in the final analysis, 17 patients (37.0%) had fT3 levels lower than the reference range. After adjustment for age, gender, and statistically important variables (NIHSS on admission, urea levels and creatinine levels), low fT3 levels were significantly associated with post-IVT sICH (p = 0.01, OR = 0.27, 95% CI 0.10–0.77) and poor functional outcomes at discharge (p = 0.04 OR = 2.58, 95% CI 1.05–6.35).

Conclusion: We found that lower free T3 levels are independently related to post-IVT sICH and poor functional outcomes at discharge in AIS patients with IVT, which should be verified and extended in large cohorts in the future.     

Argatroban plus aspirin versus aspirin in acute ischemic stroke

Objectives: Anticoagulant therapy in the acute phase of AIS remains controversial. The aim of this study was to investigate whether argatroban benefited early stroke outcomes compared with antiplatelet treatment.

Methods: We reviewed data from 1,485 patients with AIS hospitalized at Tianjin Union Medical Center (TUMC) between 1 January 2013 and 31 December 2015 from the TUMC registry database. Patients were divided into two groups: an antiplatelet group (aspirin 300 mg daily) and an argatroban group (argatroban 60 mg for 2 days followed by 20 mg daily; or 20 mg daily – both regimens combination with aspirin 100 mg daily). Two primary outcomes, change in NIHSS score (baseline–discharge) and intracerebral hemorrhage, were investigated.

Results: No major symptomatic intracerebral hemorrhages were observed in either group. Both groups had significantly decreased NIHSS scores at discharge (Z = ?14.617, P < 0.001 and Z = ?6.385, P < 0.001, respectively), and there were no significant group differences in NIHSS score change (Z = ?1.888, P = 0.059). In the mild stroke subgroup, the argatroban group had a worse NIHSS score at discharge (Z = ?6.148, P = 0.002), while the aspirin group had an improved NIHSS score (Z = ?4,423, P < 0.001). In the moderate stroke subgroup, both groups had significantly decreased NIHSS scores at discharge (Z = ?13.260, P < 0.001 and Z = ?7.108, P < 0.001, respectively) and there were no significant group differences in NIHSS score changes (Z = ?1.888, P = 0.059).

Conclusion: Argatroban is effective and safe for the treatment of moderate AIS with similar efficacy to high-dose aspirin in the acute phase of AIS, although no additional benefit on short-term outcome was observed. For patients with mild AIS, argatroban may be inferior to high-dose aspirin.     

The Effect of Therapeutic Mild Hypothermia on Brain Microvascular Endothelial Cells During Ischemia–Reperfusion Injury

Background

To determine the cerebral protective effects of mild hypothermia (MH) on cerebral microcirculation.

Methods

We established ischemia–reperfusion (I/R) injury and MH treatment models with rat brain microvascular endothelial cells (RBMECs) in vitro and examined the apoptotic changes. The cultured RBMECs were randomly divided into the control group, I/R group, and MH group, which was further divided into two subgroups: intra-ischemia hypothermia (IIH) and post-ischemia hypothermia (PIH). Cell morphological changes were assessed using fluorescence microscopy. Apoptotic rates were obtained by flow cytometry. Expressions of caspase-3, Bax, and Bcl-2 were analyzed by Western blot.

Results

I/R injury in vitro induced apoptosis of RBMECs. The apoptotic rates in the control group, I/R group, and MH group were 0.13, 19.04, and 13.13%, respectively (P < 0.01). Compared with the I/R group, the MH group showed a significant decrease in the number of apoptotic cells, mainly in stage I apoptotic cells (P < 0.0083). The caspase-3 and Bax expressions were significantly enhanced (P < 0.05) in RBMECs after I/R injury, while substantial decreases in Bcl-2 expression were noted (P < 0.05). Following MH intervention, the increase in caspase-3 and Bax expression was suppressed (P < 0.05), while Bcl-2 expression significantly increased. The apoptotic rates or protein expressions between the two subgroups were not different significantly (P > 0.05).

Conclusions

These results indicate that MH could inhibit RBMEC apoptosis by preventing pro-apoptotic cells and early apoptotic cells from progressing to intermediate and advanced stages. This may be due to the effect of MH on I/R-induced apoptotic gene expression changes.

     

Efficacy of elaborated semantic features analysis in Aphasia: a quasi-randomised controlled trial

ABSTRACT

Background: Word finding difficulty is one of the most common features of aphasia. Semantic Features Analysis (SFA) directly aims to improve word finding in people with aphasia. Evidence from systematic reviews suggests that SFA leads to positive outcomes, yet the evidence comprises single case studies and case series. There is a need to evaluate the efficacy of SFA in controlled group studies/trials.

Aims: To evaluate the efficacy of Elaborated Semantic Feature Analysis (ESFA) for word finding in people with aphasia. We investigated: (a) the efficacy of ESFA versus a delayed therapy/control, (b) the efficacy of two therapy approaches – individual versus a combination of individual and group therapy.

Methods and procedures: We ran a multi-centre, quasi-randomised controlled trial, nested in a larger study (Thales-Aphasia). Participants were recruited from community settings. They had to be people with aphasia due to stroke at least four months post-onset. Participants were randomized to individual vs combination vs delayed therapy/control groups. Both therapy groups had 3 h of ESFA per week for 12 weeks. Delayed therapy/control group had no intervention for 12 weeks and were then randomized to either individual or combination therapy. The primary outcome was confrontation naming. Secondary outcomes were the Boston Naming Test, Discourse, the Functional Assessment of Communication Skills for adults (ASHA–FACS), the Stroke and Aphasia Quality of Life scale (SAQOL-39g), the General Health Questionnaire-12 item, and the EQ-5D.

Outcomes and Results: Of the 72 participants of the Thales-Aphasia project, 58 met eligibility criteria for speech-language therapy and 39 were allocated to ESFA. The critical p-value was adjusted for multiple comparisons (.005). For the therapy versus control comparison, there was a significant main effect of time on the primary outcome (p < .001, η²_p = .42) and a significant interaction effect (p = .003, η²_p = .21). An interaction effect for the SAQOL-39g (p = .015, η²_p = .11) and its psychosocial domain (p = .013, η²_p = .12) did not remain significant after Bonferroni adjustment. For the individual versus combination ESFA comparison, there were significant main effects of time on the primary outcome (p < .001, η²_p = .49), the BNT (p < .001, η²_p = .29) and the ASHA-FACS (p = .001, η²_p = .18). Interaction and group effects were not significant.

Conclusion: Though underpowered, this study provides evidence on the efficacy of ESFA to improve word finding in aphasia, with gains similar in the two therapy approaches.     

Oxytocin provides protection against diabetic polyneuropathy in rats

Purpose: The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats.

Materials and methods: Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naïve control group and received no drug (n = 6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1 ml/kg saline or 80 μg/kg OT or 160 μg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed.

Results: Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 μg/kg OT significantly improved EMG findings. OT treatment significantly lessened the thickening of perineural fibrosis when compared with saline group (p < 0.001). Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline-treated rats showed considerable increase in bax, caspase 3 and caspase 8 expressions (p < 0.001) while OT treatment significantly suppressed these apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to saline group.

Conclusion: Present results demonstrate that OT appears to alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing inflammation, oxidative stress and apoptotic pathways.     

Effects of group versus individual therapy for patients with memory disorder after an acquired brain injury: A randomized,controlled study

Introduction: This randomized, controlled, single-blind study compared the efficacy of group versus individual memory rehabilitation therapy for patients with acquired brain injury (ABI). Subjects (N = 65) were assigned to individual (IT), group (GT), or no (NT) therapy during the three-week rehabilitation program. A neuropsychological assessment was conducted before treatment, immediately after completing treatment, and 4 months after completing treatment. Three levels of functioning were assessed: participation, disability, and impairment. The primary outcome measure was the Rivermead Behavioural Memory Test (RBMT). The results of the cognitive measures in the three groups at subsequent assessments were compared, and the effect sizes were calculated to investigate the magnitude of improvement.

Results: There were no significant changes in self-reported patient memory problems for the participation-level measures. However, relatives of participants in the GT group reported a decreased frequency of memory failures (p = .026). According to the ability-level measure (RBMT), both therapeutic groups had similar significant improvements (p < .001), and the effect sizes were large in both groups. Although the NT group also improved (p = .015), the effect size was small. The differences between the three groups were not significant according to analysis of variance (ANOVA). However, after therapy was completed, only the GT group continued to improve (p = .013). For the impairment-level measures, the IT group showed significant improvement post treatment in three out of four measures (p < .05). This group had medium effect sizes, while the other groups showed a small or marginal effect.

Conclusions: Cognitive rehabilitation – either in a group or individually – led to equally enhanced memory functioning in ABI patients, but the effects were not significantly different from those for patients in the NT group. GT and IT had specific effects on different levels of functioning.     

Independently ambulant,community–dwelling stroke survivors have reduced cardiorespiratory fitness,mobility and knee strength compared to an age- and gender-matched cohort

Background: Most exercise interventions for stroke survivors are designed for those who have substantial motor and functional disabilities. There remains a group of well-recovered stroke survivors who have yet to be investigated in terms of their physical capacity and fitness levels.

Objective: To assess and compare the physical capacities of independently ambulant, community-dwelling stroke survivors to age- and gender-matched comparison participants.

Methods: Data were obtained from 17 stroke survivors participating in the How FITSS? Trial, all with functional ambulatory category of ≥4 and a self-selected walking speed ≥0.8 m s^?1. An additional 17 healthy control participants were recruited. Cardiorespiratory fitness (CRF) was measured using oxygen consumption (VO_2peak), and additional measures of walking speed (m s^?1), leg strength and body composition were also assessed. Differences between groups were assessed by matched pairs t-tests. Effect sizes were calculated using Cohen’s d.

Results: There were no significant differences in age, BMI, muscle mass or body fat between groups (p > 0.05). Peak VO₂ was lower in the stroke group for the shuttle walk test (p = 0.037) and progressive cycle test (p = 0.019), as were all CRF test performance measures (p < 0.05). Stroke survivors walked significantly (p < 0.001) slower at both self-selected and fast speeds. Effect sizes of group differences for all leg strength variables were medium to large, with peak torque lower in the stroke group for all trials.

Conclusions: Despite being independently ambulant and community dwelling, the CRF, walking speed and leg strength of this group were reduced compared to non-stroke comparison participants. These patients may benefit from undertaking targeted exercise programmes.