Effects of the suppression of 5-HT1A receptors in the left, right, or bilateral basolateral amygdala on memory consolidation in chronic stress in male rats.

The serotonin-1A receptors (5-HT1A) in the two cerebral hemispheres are differentially involved in memory. The distribution of 5-HT1A receptors in the left and right amygdala is different. Furthermore, evidence shows that the 5-HT1A receptors in the left and right amygdala work differently in memory function. The basolateral amygdala (BLA) also regulates hippocampal long-term potentiation (LTP) during stress. However, which BLA structure in each hemisphere underlies such lateralized function is unclear. The present research investigated the possible involvement of 5-HT1A lateralization in the BLA on stress-induced memory impairment. 5-HT1A receptor antagonist (Way-100-635) was injected into the left, right, or bilateral BLA twenty minutes before chronic restraint stress (CRS) for 14 consecutive days. Results indicated that suppression of 5HT1A-receptors in the BLA plays an essential role in reducing the acquisition of passive avoidance in the shuttle box test and spatial memory in the Barnes maze test in the stress animals. This decrease was significant in the CRS animals with left and bilateral suppressed 5HT1A-receptors in the BLA. Field potential recording results showed that the left, right, and bilateral injection of Way-100-635 into the BLA significantly reduced the slope and amplitude of fEPSP in the CA1 area of the hippocampus in stressed rats. No significant difference was observed in neuronal arborization in the CA1 area of the hippocampus. In conclusion, the 5-HT1A receptor in the left and right sides of BLA nuclei play a different role in memory consolidation in the hippocampus under stress.

Biochemical Mechanisms of Beneficial Effects of Beta-Alanine Supplements on Cognition.

Using nutritional interventions to cure and manage psychiatric disorders is a promising tool. In this regard, accumulating documents support strong relationships between the diet and brain health throughout the lifespan. Evidence from animal and human studies demonstrated that ß-alanine (Beta-alanine; BA), a natural amino acid, provides several benefits in fight against cognitive decline promoting mental health. This review summarizes and reports state-of-the-art evidence on how BA affects cognitive health and argues existence of potential unrevealed biochemical mechanisms and signaling cascades. There is a growing body of evidence showing that BA supplement has a significant role in mental health mediating increase of the cell carnosine and brain-derived neurotrophic factor (BDNF) content. BDNF is one of the most studied neurotrophins in the mammalian brain, which activates several downstream functional cascades via the tropomyosin-related kinase receptor type B (TrkB). Activation of TrkB induces diverse processes, such as programmed cell death and neuronal viability, dendritic branching growth, dendritic spine formation and stabilization, synaptic development, cognitive-related processes, and synaptic plasticity. Carnosine exerts its main effect via its antioxidant properties. This critical antioxidant also scavenges hypochlorous acid (HOCl), another toxic species produced in mammalian cells. Carnosine regulates transcription of hundreds of genes related to antioxidant mechanisms by increasing expression of the nuclear erythroid 2-related factor 2 (Nrf2) and translocating Nrf2 to the nucleus. Another major protective effect of carnosine on the central nervous system (CNS) is related to its anti-glycating, anti-aggregate activities, anti-inflammatory, metal ion chelator activity, and regulation of pro-inflammatory cytokine secretion. These effects could be associated with the carnosine ability to form complexes with metal ions, particularly with zinc (Zn2+). Thus, it seems that BA via BDNF and carnosine mechanisms may improve brain health and cognitive function over the entire human lifespan.

Comparative effects of the alcoholic extract of Terminalia chebula and crocin on stress­induced anxiety­like behavior and memory impairment in male rats.

Crocin and Terminalia chebula (T. chebula) were proven to have neuroprotective effects. In this study, we evaluated the preventive effects of crocin and alcoholic extract of the T. chebula alone and in combination to examine their efficacy against chronic restraint stress (CRS)­induced cognitive impairment, anxiety­like behaviors, hippocampal synaptic plasticity deficit as well as neuronal arborization damage in the hippocampal CA1 neurons. Over 14 consecutive days, animals received crocin, T. chebula, or their combination (5 min before CRS). The elevated plus­maze results showed that crocin and T. chebula alone and in combination treatment significantly increased the time spent in open arms, percentage of open arm entries, and head dipping as compared with the CRS group. Barnes maze results showed that administration of crocin and T. chebula alone and their combination significantly improves spatial memory indicators such as distance traveled, latency time to achieving the target hole, and the number of errors when compared to the CRS group. These learning deficits in CRS animals correlated with a reduction of long-term potentiation (LTP) in hippocampal CA1 synapses, which both T. chebula and crocin treatment improved field excitatory postsynaptic potentials (fEPSP) amplitude and fEPSP slope reduction induced by CRS. Golgi­Cox staining showed that T. chebula and crocin treatment increased the number of dendrites and soma arbors in the CA1 neurons compared with the CRS group. Our results suggest that both T. chebula and crocin attenuated CRS­induced anxiety­like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons. We found no significant difference between single treatments of T. chebula or crocin and their combination in protecting CRS­induced anxiety­like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons.

The Complexity of Electroencephalographic Signal Decreases during the Social Stress.

Social stress affects brain function. Trier social stress test (TSST) is a standard test to assess it. The study aimed to analyze the electroencephalographic (EEG) recording during and after TSST in healthy subjects. The EEG signals of 44 healthy men participating in the study were recorded in the control condition, during and after TSST and after 30 min of recovery. Salivary cortisol (SC) and the Emotional Visual Analog Scale (EVAS) score were measured in the control condition, after TSST, and after the recovery period. The false discovery rate correction was used to control the false positive of significance in EEG. In the comparison control condition, the SC and EVAS levels significantly increased after TSST. The relative Delta band frequency significantly increased during TSST. On the other hand, the Beta bands and, in less amount, the Theta and Gamma 1 (30-40 Hz) oscillations decreased, especially in the frontal region. The nonlinear features such as, approximate and spectral entropy, Katz fractal dimension behaved like Beta band oscillation. All changes returned to baseline after TSST except the increase of Katz in the F3 channel after the recovery period. Thus, stress on EEG increased low frequency (1-4 Hz), decreased high frequency (13-40 Hz), and complexity indices during TSST.

Date palm spathe extract reverses chronic stress-induced changes in dendritic arborization in the amygdala and impairment of hippocampal long-term potentiation.

Chronic restraint stress induces anxiety-like behaviors and emotional abnormalities via an alteration of synaptic remodeling in the amygdala and the hippocampus. Given that the date palm spathe has been shown to have neuroprotective effects on different experimental models, this study aimed to address whether the date palm spathe extract (hydroalcoholic extract of date palm spathe [HEDPP]) can reduce chronic restraint stress-induced behavioral, electrophysiological, and morphological changes in the rat model. Thirty-two male Wistar rats (weight 200-220 g) were randomly divided into control, stress, HEDPP, and stress + HEDPP for 14 days. Animals were submitted to restraint stress for 2 h per day for 14 consecutive days. The animals of the HEDPP and stress + HEDPP groups were supplemented with HEDPP (125 mg/kg) during these 14 days, 30 min before being placed in the restraint stress tube. We used passive avoidance, open-field test, and field potential recording to assess emotional memory, anxiety-like behavioral and long-term potentiation in the CA1 region of the hippocampus, respectively. Moreover, Golgi-Cox staining was used to investigate the amygdala neuron dendritic arborization. Results showed that stress induction was associated with behavioral changes (anxiety-like behavioral and emotional memory impairment), and the administration of HEDPP effectively normalized these deficits. HEDPP remarkably amplified the slope and amplitude of mean-field excitatory postsynaptic potentials (fEPSPs) in the CA1 area of the hippocampus in stressed rats. Chronic restraint stress significantly decreased the dendritic arborization in the central and basolateral nucleus of the amygdala neuron. HEDPP suppressed this stress effect in the central nucleus of the amygdala. Our findings indicated that HEDPP administration improves stress-induced learning impairment and memory and anxiety-like behaviors by preventing adverse effects on synaptic plasticity in the hippocampus and amygdala.

Brain-derived Neurotrophic Factor and High Sensitive C-reactive Protein in Bipolar Depression and Unipolar Depression: The Practical Usage as a Discriminatory Tool.

Objective: Brain-derived neurotrophic factor (BDNF) and high sensitive C-reactive protein (hs-CRP) have been reported to play roles in depression and bipolar disorder (BD). However, the probable discriminatory properties of these biologic markers are less investigated. We aimed to assess the serum BDNF and hs-CRP levels among Iranian patients with major depressive disorder (MDD) and BD during a depressive episode and investigate the optimum cut-off point for differential diagnosis of BD and MDD. Methods: We recruited 30 patients with MDD, 30 with BD in depressive mood and 30 healthy comparators. Blood sample was taken from each participant to measure BDNF and hs-CRP levels. We also used receiver operating characteristic (ROC) curve analysis to find an optimal cut-off point for differentiating MDD from BD according to pre-defined variables. Results: The mean age of total study population was 37.3 ± 5.0 years (males: 49%). BDNF was significantly lower in patients with BD, followed by MDD subjects and healthy controls 541.0 ± 601.0 pg/ml vs. 809.5 ± 433.3 pg/ml vs. 1,482.1 ± 519.8, respectively, p < 0.001). The area under curve of ROC curve analysis for BD versus MDD was 0.704 (95% confidence interval: 0.564-0.844, p = 0.007). We also found that the BDNF cut-off value of 504 could appropriately distinguished BD from MDD (sensitivity: 73%, specificity: 70%). No significant association were identified in terms of hs-CRP levels. Conclusion: Patients suffering from BD had lowest BDNF levels compared to MDD or healthy adults and this biomarker could play a practical role differentiating MDD from BD. Several studies are required confirming our outcomes.

Changes in psychological and cognitive variables as well as cortisol levels in recovered Covid-19 patients: a longitudinal study.

BACKGROUND: Decreased psychological and cognitive functioning is one of the complications of Covid-19 disease. We aimed to evaluate mental health, cognitive functioning, and salivary cortisol levels in Covid-19 patients with different disease severities in three 45-day intervals after recovery. METHODS: 258 Covid-19 patients were assigned into three groups based on their disease severity: 112 patients in mild group, 67 patients in moderate group and 79 patients in severe group. The participants underwent psychological evaluations (including Depression, Anxiety and Stress Scale questionnaire, Beck Depression Inventory, SpeilBerger State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Inventory), cognitive assessments (The Paced Auditory Serial Addition Test) and salivary cortisol level evaluation in three 45-day periods. Non-parametric statistical methods were applied for psychological and cognitive indicators, while two-way mixed model ANOVA was used to evaluate the cortisol concentration in three replications. RESULTS: The group of mild patients became more anxious and the group of moderate patients became more anxious and depressed. But all three groups of patients developed severe sleep disorders over time. For cognitive functioning, although the results showed a decrease in the correct response rate, a significant increase in the correct response rate was observed in all three groups in all three measurements. However, the response speed not only did not increase, but also decreased in severe group. Cortisol level had a markedly increasing trend in all three groups. CONCLUSION: Improvement of cognitive functioning was in line with the increase in cortisol. Besides, the decrease in mental health had no effect on the cognitive functioning.

Adrenal histological and functional changes after hepatic encephalopathy: From mice model to an integrative bioinformatics analysis.

Hepatic encephalopathy (HE), which is caused by neurotoxin agents in the liver, is a complicated condition with a variety of neurological manifestations. Recently, endocrine alterations have been more paid attention to for neurological severity in the course of HE, e.g. adrenal gland. To identify the role of adrenal gland in the context of HE, we evaluated the functional changes of adrenal gland (i.e., plasma corticosterone concentrations and histopathological changes) in mice model of HE. To dig deep into the molecular and genetic underpinnings, a comprehensive enrichment analysis for shared genes between HE and adrenal insufficiency (AI) was also performed. Our results showed a significant reduction in the level of plasma corticosterone and severe cellular necrosis in zona fasciculate of adrenal cortex, possibly indicating adrenal insufficiency. Enrichment analysis indicated four common genes, besides predicted five novel genes and some significant MicroRNAs (miRNAs) and transcription factors for both HE and AI. Couples with, several biological processes, such as DNA damage, inflammatory responses, glycolytic processes, and insulin receptor signaling pathway were predicted in both HE and AI. To sum up, data from experimental tests and bioinformatics analyses suggest that AI play an important role in the pathogenesis and progression of HE.

A major depressive disorder diagnosis approach based on EEG signals using dictionary learning and functional connectivity features.

Major depressive disorder (MDD) as a psychiatric illness negatively affects the behavior and daily life of the patients.Therefore, the early MDD diagnosis can help to cure the patients more efficiently and prevent adverse effects, although its unclear manifestations make the early diagnosis challenging. Nowadays, many studies have proposed automatic early MDD diagnosis methods based on electroencephalogram (EEG) signals. This study also presents an automated EEG-based MDD diagnosis framework based on Dictionary learning (DL) approaches and functional connectivity features. Firstly, a feature space of MDD and healthy control (HC) participants were constructed via functional connectivity features.Next, DL-based classification approaches such as Label Consistent K-SVD (LC-KSVD) and Correlation-based Label Consistent K-SVD (CLC-KSVD) methods, were utilized to perform the classification task. A public dataset was used, consisting of EEG signals from 34 MDD patients and 30 HC subjects, to evaluate the proposed method. To validate the proposed method, 10-fold cross-validation technique with 100 iterations was employed, providing accuracy (AC), sensitivity (SE), specificity (SP), F1-score (F1), and false discovery rate (FDR) performance metrics. The results show that LC-KSVD2 and CLC-KSVD2 performed efficiently in classifying MDD and HC cases. The best classification performance was obtained by the LCKSVD2 method, with average AC of 99.0%, SE of 98.9%, SP of 99.2%, F1 of 99.0%, and FDR of 0.8%. According to the results, the proposed method provides an accurate performance and, therefore, it can be developed into a computer-aided diagnosis (CAD) tool for automatic MDD diagnosis.

Laterality dissociation of ventral hippocampus inhibition in learning and memory, glial activation and neural arborization in response to chronic stress in male Wistar rats.

Many studies suggest that animals exhibit lateralized behaviors during stressful situations. However, which brain structure in each hemisphere underlies such lateralized function is unclear. This study, investigated the effects of bilateral and unilateral inhibition of the ventral hippocampus (VH) on chronic restraint stress (CRS) induced memory impairment. Unilateral and bilateral VH cannulation was carried out. After a week of recovery, lidocaine hydrochloride was injected into the rat VH ten minutes before CRS induction for seven consecutive days. Behavioral (Y-maze and Morris water maze; MWM)), and histological (glial fibrillary acidic protein; GFAP, ionized calcium-binding adapter protein-1; Iba-1, as well as Golgi-Cox staining in the VH) studies were performed. The result showed no significant difference between the effect of right-only and left-only of VH inhibition induced by lidocaine on spatial learning and memory and working memory. In addition, lidocaine treated groups were significantly lower in spatial learning and memory and working memory than control groups during non-stress conditions. Furthermore, the dendritic arborization in the right-only, left-only and bilateral VH microinjected lidocaine significantly decreased after the CRS condition compared with the control group. However, lidocaine microinjection resulted in up-regulation levels of GFAP and Iba1 in the right-only, left-only and bilateral of VH and they were higher significantly than that of their control groups after CRS and during non-stress condition. Meanwhile, there is no significant difference between the effect of right-only and left-only of VH inhibition on neuronal arborization and glial cells during non-stress and after the CRS condition. In conclusion, bilateral VH inhibition can give rise to increase CRS-induced memory impairment. These findings were accompanied by elevating GFAP and Iba1 while reducing the dendritic arborization.

A major depressive disorder classification framework based on EEG signals using statistical, spectral, wavelet, functional connectivity, and nonlinear analysis.

BACKGROUND: Major depressive disorder (MDD) is a prevalent mental illness that is diagnosed through questionnaire-based approaches; however, these methods may not lead to an accurate diagnosis. In this regard, many studies have focused on using electroencephalogram (EEG) signals and machine learning techniques to diagnose MDD. NEW METHOD: This paper proposes a machine learning framework for MDD diagnosis, which uses different types of EEG-derived features. The features are extracted using statistical, spectral, wavelet, functional connectivity, and nonlinear analysis methods. The sequential backward feature selection (SBFS) algorithm is also employed to perform feature selection. Various classifier models are utilized to select the best one for the proposed framework. RESULTS: The proposed method is validated with a public EEG dataset, including the EEG data of 34 MDD patients and 30 healthy subjects. The evaluation of the proposed framework is conducted using 10-fold cross-validation, providing the metrics such as accuracy (AC), sensitivity (SE), specificity (SP), F1-score (F1), and false discovery rate (FDR). The best performance of the proposed method has provided an average AC of 99%, SE of 98.4%, SP of 99.6%, F1 of 98.9%, and FDR of 0.4% using the support vector machine with RBF kernel (RBFSVM) classifier. COMPARISON WITH EXISTING METHODS: The obtained results demonstrate that the proposed method outperforms other approaches for MDD classification based on EEG signals. CONCLUSIONS: According to the obtained results, a highly accurate MDD diagnosis would be provided using the proposed method, while it can be utilized to develop a computer-aided diagnosis (CAD) tool for clinical purposes.

The controlling role of nitric oxide within the shell of nucleus accumbens in the stress-induced metabolic disturbance.

CONTEXT AND OBJECTIVES: The involvement of the nitricergic system within the shell part of the nucleus accumbens (NAc) was evaluated in the metabolic disturbances due to stress. MATERIALS AND METHODS: Male Wistar rats were cannulated in the shell of the left NAc. They received either saline or different doses of L-arginine and/or L-NAME five minutes before each stress session, for four days. Plasma cortisol concentration, food and water intake, time elapsing for eating, animal weight changes and adrenal gland weight were recorded. RESULTS: The L-arginine 1 µg/rat decreased the level of cortisol, water and food intake and time of feeding and increased the adrenal weight. But L-NAME at 1 µg/rat had opposite effects on these factors. However, the drugs showed similar effects at 10 µg/rat. CONCLUSION: Injection of nitric oxide modifiers into the left side of NAc shell part may have an interactive role with sub-chronic stress in metabolic behaviour.

Crocin attenuates the granular cells damages on the dentate gyrus and pyramidal neurons in the CA3 regions of the hippocampus and frontal cortex in the rat model of Alzheimer's disease.

Amyloid ß-peptides (Aß) are considered as a major hallmark of Alzheimer's disease (AD) that can induce synaptic loss and apoptosis in brain regions, particularly in the cortex and the hippocampus. Evidence suggests that crocin, as the major component of saffron, can exhibit neuromodulatory effects in AD. However, specific data related to their efficacy to attenuate the synaptic loss and neuronal death in animal models of AD are limited. Hence, we investigated the efficacy of crocin in the CA3 and dentate gyrus (DG) regions of the hippocampus and also in frontal cortex neurons employing a rat model of AD. Male Wistar rats were randomly divided into control, sham, AD model, crocin, and AD model + crocin groups, with 8 rats per group. AD model was established by injecting Aß1-42 into the frontal cortex rats, and thereafter the rats were administrated by crocin (30 mg/kg) for a duration of 12-day. The number of live cells, neuronal arborization and apoptosis were measured using a Cresyl violet, Golgi-Cox and TUNEL staining, respectively. Results showed that, the number of live cells in the hippocampus pyramidal neurons in the CA3 and granular cells in the DG regions of the AD rats significantly decreased, which was significantly rescued by crocin. Compared with the control group, the axonal, spine and dendrites arborization in the frontal cortex and CA3 region of the AD model group significantly decreased. The crocin could significantly reverse this arborization loss in the AD rats (P < 0.05). The apoptotic cell number in the CA3 and DG regions in the AD model group was significantly higher than that of the control group (P < 0.05), while crocin significantly decreased the apoptotic cell number in the AD group (P < 0.05). Conclusion. Crocin can improve the synaptic loss and neuronal death of the AD rats possibly by reducing the neuronal apoptosis.

Simvastatin and bone marrow-derived mesenchymal stem cells (BMSCs) affects serum IgE and lung cytokines levels in sensitized mice.

INTRODUCTION: The effects of bone marrow-derived mesenchymal stem cells (BMSCs) and simvastatin combination therapy on serum total and specific IgE levels and lung IL-13 and TGF-ß levels in sensitized mouse were examined. MATERIAL AND METHODS: Control (n = 5), Sensitized (S), (n = 5), S + BMSC (n = 6), S + simvastatin (n = 6) and S + BMSC + simvastatin (n = 4) groups of BALB/c mice were studied. Mice were sensitized by ovalbumin. Sensitized mice were treated with a single intravenous injection of BMSCs (1 × 106) or daily intraperitoneal injection of simvastatin (40 mg/kg) or both BMSCs and simvastatin on the last week of challenge. Serum total and ovalbumin specific IgE levels as well as IL-13 and TGF-ß levels in broncho-alveolar lavage (BAL) fluid were evaluated. RESULTS: Serum total and specific IgE levels as well as lung IL-13 and TGF-ß levels were significantly increased in S group compared to control group (P < 0.001 for all cases). Treatment with BMSCs, simvastatin and their combination significantly decreased serum total and specific IgE levels (P < 0.05 to P < 0.01). However, IL-13 and TGF-ß levels were significantly decreased by BMSCs and BMSC + simvastatin combination therapy (P < 0.05 for all cases). The effect of simvastatin and BMSCs combination therapy on serum specific IgE levels as well as lung IL-13 and TGF-ß levels were significantly higher than the effect of BMSCs and simvastatin alone (P < 0.001 for IL-13 and P < 0.01 for other cases). CONCLUSIONS: Simvastatin and BMSCs combination therapy affects serum IgE as well as lung IL-13 and TGFß levels more than BMSC therapy and simvastatin therapy alone which may be due to increased BMSCs migration into the lung tissue.

Deep brain stimulation in a rat model of post-traumatic stress disorder modifies forebrain neuronal activity and serum corticosterone.

OBJECTIVES: Post-traumatic stress disorder (PTSD), one of the most devastating kinds of anxiety disorders, is the consequence of a traumatic event followed by intense fear. In rats with contextual fear conditioning (CFC), a model of PTSD caused by CFC (electrical foot shock chamber), deep brain stimulation (DBS) alleviates CFC abnormalities. MATERIALS AND METHODS: Forty Male Wistar rats (220-250 g) were divided into 5 groups (n=8) and underwent stereotactic surgery to implant electrodes in the right basolateral nucleus of the amygdala (BLn). After 7 days, some animals received a foot shock, followed by another 7-day treatment schedule (DBS treatment). Next, freezing behavior was measured as a predicted response in the absence of the foot shock (re-exposure time). Blood serum corticosterone levels and amygdala c-Fos protein expression were assessed using Enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively. Furthermore, freezing behaviors by re-exposure time test and general anxiety by elevated plus-maze (EPM) were evaluated. RESULTS: PTSD decreased serum corticosterone levels and increased both amygdala c-Fos expression and freezing behaviors. Therefore, DBS treatment significantly (P<0.001) enhanced serum corticosterone levels and could significantly (P<0.001) reduce both c-Fos protein expression and freezing behaviors' duration. However, DBS treatment has no effect on the general anxiety in PTSD rats. CONCLUSION: We argue that these outcomes might demonstrate the mechanism of DBS treatment, a complete therapeutic strategy, in PTSD patients.

Evaluation of Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cell Combination Therapy on Airway Remodeling in a Mouse Asthma Model.

INTRODUCTION: The effect of bone marrow-derived mesenchymal stem cells (BMSCs) on asthma treatment was shown in our previous study. Several studies have shown the effect of statins on BMSC preservation and migration to sites of inflammation. In this study, the effects of simvastatin and BMSC combination therapy in an ovalbumin-induced asthma model in mouse were examined. METHODS: Four groups of BALB/c mice were studied including control group (animals were not sensitized), asthma group (animals were sensitized by ovalbumin), asthma + simvastatin group (asthmatic animals were treated with simvastatin), and asthma + BMSC + simvastatin group (asthmatic animals were treated with simvastatin and BMSCs). BMSCs were isolated, characterized, labeled with BrdU, and transferred into asthmatic mice. BMSC migration, airways histopathology, and total and differential white blood cell (WBC) count in bronchoalveolar lavage (BAL) fluid were evaluated. RESULTS: A significant increase in the number of BrdU-BMSCs was found in the lungs of mice treated with simvastatin + BMSCs compared to mice treated with BMSCs. The histopathological changes, BAL total WBC counts, and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with simvastatin significantly decreased airway inflammation and inflammatory cell infiltration. Combination therapy improved all measured parameters higher than simvastatin. Goblet cell hyperplasia and subepithelial fibrosis were also decreased in combination therapy group. CONCLUSION: These results indicated that simvastatin and BMSC combination therapy was superior to simvastatin therapy and BMSC therapy alone in reduction of airway remodeling and lung inflammation in the ovalbumin-induced asthma model in mouse.

Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse.

OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BMSCs) have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined. MATERIALS AND METHODS: BALB/c mice were divided into three groups: control group (animals were not sensitized), asthma group (animals were sensitized by ovalbumin), asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs). BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU). After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC) count in bronchoalveolar lavage (BAL) fluid were evaluated. RESULTS: A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia. CONCLUSION: The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse.