Crocin nano-chitosan-coated compound improves anxiety disorders, learning, and spatial memory in Alzheimer's model induced by beta-amyloid in rats.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disease that results in the gradual breakdown of brain tissue, causing the deterioration of intellectual function and ability. Crocin is a saffron carotenoid compound proven to have excellent neuroprotective and anti-inflammation properties, although it has some limitations such as low stability and bioavailability. Therefore, in the current research, we tried to improve these limitations by using nanotechnology and chitosan as the carrier. Our study examined the therapeutic effects of crocin nano-chitosan-coated compound and compared it with intact crocin in lower dosages than other studies in AD rat models. Materials and Methods: Encapsulating crocin into chitosan nanoparticles was done through a modified technique to improve its limitations. The AD rat model was induced by bilaterally injecting beta-amyloid (Aß) peptide into the frontal lobe using a stereotaxic device. To evaluate memory, we conducted the Barnes maze test, and to evaluate anxiety, we used the elevated plus maze test. Also, histological tests were conducted to evaluate neuronal damage in each group. Results: Crocin nano-chitosan-coated administration significantly improved specific memory indicators compared to the Aß and other treated groups. A significant decrease in anxiety indicators was detected compared to the Aß and other treated groups. Finally, the results of hippocampus staining indicated a meaningful difference between the Aß group and other treated groups, compared to the crocin nano-chitosan-coated group. Conclusion: Treatment with low dosages of crocin in the nano-coated form exhibited great efficacy in reducing AD's adverse effects compared to the same dosage of intact crocin.

Auditory Steady-State Evoked Potentials in Post Traumatic Stress Disorder: Introduction of a Potential Biomarker.

Objective: The lack of steady-state evoked potential (SSEP) studies on post-traumatic stress disorder (PTSD) has led to undiscovered useful information about the pathophysiology of the disorder. Thus, we explored SSEP patterns in PTSD patients during a stop-signal task to disclose possible impairments in these informative brain potentials. Method : 25 adult patients with PTSD and 25 healthy adults participated in this research. Subjects were assessed with electroencephalography while the tone signal stimuli at 40 Hz were used to evoke SSEPs and subjects performed a stop-signal task. The amplitude and phase of SSEPs were then computed in different brain regions. The subjects were also evaluated using the Mississippi PTSD questionnaire. Appropriate statistical methods such as repeated measure ANOVA were used to compare the two groups, and the correlation between SSEPs and clinical symptoms was assessed using Pearson correlation analysis. Results: Patients showed considerably poorer performance in the cognitive task (P < 0.01), accompanied by raised SSEP phase and amplitude in the anterior and midline regions compared to healthy controls (P < 0.05). The Mississippi total score was positively correlated with the SSEP amplitude in the midline region (r = 0.62, P < 0.05). Furthermore, based on ROC analysis, the SSEP amplitude in the midline region provided an excellent AUC value (AUC = 0.850) for distinguishing patients with PTSD from normal subjects. Conclusion: Current findings suggest that abnormalities in the anterior and midline cortical neural networks are involved in the pathophysiology of PTSD. Importantly, midline abnormalities may provide a clinically-relevant measure for researchers wishing to assess the use of biomarkers for early diagnosis of PTSD as well as to evaluate new therapeutic and management approaches in the treatment of PTSD.

Lateralization of the 5-HT1A receptors in the basolateral amygdala in metabolic and anxiety responses to chronic restraint stress.

Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT1A receptor) lateralization in the basolateral amygdala (BLA) in vivo on anxiety and metabolic behaviors under stress. In the present study, the effect of unilateral and bilateral suppression of the 5-HT1A receptor in the BLA on anxiety, and metabolic responses to chronic restraint stress was assessed. Male Wistar rats 7 days after cannulation into the BLA received chronic restraint stress for 14 consecutive days. 20 minutes before induction of stress, WAY-100-635 (selective 5-HT1A antagonist) or sterile saline (vehicle) was administered either uni- or bi-laterally into the BLA. Behavioral (elevated plus maze; EPM, and open field test), and metabolic parameter studies were performed. Results showed that stress causes a significant increase in weight gain compared to control. In the non-stress condition, the left and bilaterally, and in the stress condition the right, left, and both sides, inhibition of 5-HT1A in the BLA reduced weight gain. In the restraint stress condition, only inhibition of the 5-HT1A receptor in the left BLA led to decreased food intake compared to the control group. In stress conditions, inhibition of the 5-HT1A receptor on the right, left, and bilateral BLA increased water intake compared to the stress group. Inhibition of the 5-HT1A receptor on the left side of the BLA by WAY-100-635 induced anxiety-like behaviors in stressed rats. Similarly, WAY-100-635 on the left BLA effectively caused anxiety-like behaviors in both EPM and open field tests in the control animals. In conclusion, it seems that 5-HT1A receptors in the left BLA are more responsible for anxiety-like behaviors and metabolic changes in responses to stress.

Investigating the Ability of Radiomics Features for Diagnosis of the Active Plaque of Multiple Sclerosis Patients.

Background: Multiple sclerosis (MS) is the most common non-traumatic disabling disease. Objective: The aim of this study is to investigate the ability of radiomics features for diagnosing active plaques in patients with MS from T2 Fluid Attenuated Inversion Recovery (FLAIR) images. Material and Methods: In this experimental study, images of 82 patients with 122 MS lesions were investigated. Boruta and Relief algorithms were used for feature selection on the train data set (70%). Four different classifier algorithms, including Multi-Layer Perceptron (MLP), Gradient Boosting (GB), Decision Tree (DT), and Extreme Gradient Boosting (XGB) were used as classifiers for modeling. Finally, Performance metrics were obtained on the test data set (30%) with 1000 bootstrap and 95% confidence intervals (95% CIs). Results: A total of 107 radiomics features were extracted for each lesion, of which 7 and 8 features were selected by the Relief method and Boruta method, respectively. DT classifier had the best performance in the two feature selection algorithms. The best performance on the test data set was related to Boruta-DT with an average accuracy of 0.86, sensitivity of 1.00, specificity of 0.84, and Area Under the Curve (AUC) of 0.92 (95% CI: 0.92-0.92). Conclusion: Radiomics features have the potential for diagnosing MS active plaque by T2 FLAIR image features. Additionally, choosing the feature selection and classifier algorithms plays an important role in the diagnosis of active plaque in MS patients. The radiomics-based predictive models predict active lesions accurately and non-invasively.

Effect of Papaver rhoeas hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced post-traumatic stress disorder.

The function of hypothalamic-pituitary-adrenal (HPA) axis and psychosocial behaviors are affected in post-traumatic stress disorder (PTSD). Based on presence of several beneficial alkaloids in Papaver rhoeas (PR) plant, we assessed the effects of PR hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced PTSD. Male NMARI mice were assigned into two main groups (control or PTSD) according to stress exposure (presence or absent of the predator). Each main group was divided into four subgroups according to treatment with the different doses of PR extract. Mice were treated intraperitoneally by PR extract at three different doses (1,5&10 mg/kg) 30 min before the beginning of test on days 1, 2&3. Corticosterone concentration determined in the blood samples on days 1, 3&21, and mice examined for the psychosocial behaviors on the third day. PTSD induction in mice by exposing to hungry predator increased blood corticosterone and changed the psychosocial and physiological behaviors. PR extract decreased blood corticosterone in PTSD mice on the third day as well as 21st day. Also, PR extract improved the psychosocial and physiological behaviors in PTSD mice. Moreover, PR extract increased blood corticosterone in control mice at a dose-response manner. PR extract is able to decrease blood corticosterone in PTSD condition and probably prevent the HPA hyperactivity in PTSD mice when exposed to the stress stimuli. Accordingly, decreased blood corticosterone by PR extract might be involved in improvement of the physiological and psychosocial behaviors in PTSD mice.

Impact of the covid-19 pandemic on the psychological status and cortisol level of multiple sclerosis patients.

This study aimed to compare the changes in psychological status and cortisol level between multiple sclerosis (MS) patients and a healthy control group (HC). One hundred and fifty-five MS patients and 165 HC subjects had completed questionnaires consisting of 36-Item short health survey (SF-36), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory-II (BDI-II), and fatigue severity score (FSS) before and after (one year from onset) COVID-19 pandemic. The salivary cortisol level was also measured again in 26 MS patients and 14 control individuals. MS patients had lower scores of mental and physical components of quality of life (MCS and PCS), but higher HAM-A, FSS, and BDII scores than HC Before and after COVID-19. There were significant changes in scores of MCS, BDI-II, HAM-A, and FSS after the COVID-19 outbreak in MS patients, but not in PCS score. In HC group, we observed significant changes in scores of MCS, BDI-II, and FSS, but not in scores of PCS and HAM-A. Compared to HC, the MS patients reported greater deterioration in the overall mental health component of their health-related quality of life, and their levels of anxiety and fatigue over the study period. The change of cortisol levels was non-significant with a small effect size.

Deep transfer learning-based fully automated detection and classification of Alzheimer's disease on brain MRI.

OBJECTIVES: To employ different automated convolutional neural network (CNN)-based transfer learning (TL) methods for both binary and multiclass classification of Alzheimer's disease (AD) using brain MRI. METHODS: Herein, we applied three popular pre-trained CNN models (ResNet101, Xception, and InceptionV3) using a fine-tuned approach of TL on 3D T1-weighted brain MRI from a subset of ADNI dataset (n = 305 subjects). To evaluate power of TL, the aforementioned networks were also trained from scratch for performance comparison. Initially, Unet network segmentedthe MRI scans into characteristic components of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The proposed networks were trained and tested over the pre-processed and augmented segmented and whole images for both binary (NC/AD + progressive mild cognitive impairment (pMCI)+stable MCI (sMCI)) and 4-class (AD/pMCI/sMCI/NC) classification. Also, two independent test sets from the OASIS (n = 30) and AIBL (n = 60) datasets were used to externally assess the performance of the proposed algorithms. RESULTS: The proposed TL-based CNN models achieved better performance compared to the training CNN models from scratch. On the ADNI test set, InceptionV3-TL achieved the highest accuracy of 93.75% and AUC of 92.0% for binary classification, as well as the highest accuracy of 93.75% and AUC of 96.0% for multiclass classification of AD on the whole images. On the OASIS test set, InceptionV3-TL outperformed two other models by achieving 93.33% accuracy with 93.0% AUC in binary classification of AD on the whole images. On the AIBL test set, InceptionV3-TL also outperformed two other models in both binary and multiclass classification tasks on the whole MR images and achieved accuracy/AUC of 93.33%/95.0% and 90.0%/93.0%, respectively. The GM segment as input provided the highest performance in both binary and multiclass classification of AD, as compared to the WM and CSF segments. CONCLUSION: This study demonstrates the potential of applying deep TL approach for automated detection and classification of AD using brain MRI with high accuracy and robustness across internal and external test data, suggesting that these models can possibly be used as a supportive tool to assist clinicians in creating objective opinion and correct diagnosis. ADVANCES IN KNOWLEDGE: We used CNN-based TL approaches and the augmentation techniques to overcome the insufficient data problem. Our study provides evidence that deep TL algorithms can be used for both binary and multiclass classification of AD with high accuracy.

The Relationship between the Severity of the COVID-19 Disease, Temperament and Psychological Factors.

Objective: The coronavirus (COVID-19) pandemic negatively affects public mental health around the world. Individuals' reactions to COVID-19 vary depending on their temperament, individual differences, and personality traits. Therefore, the current study is conducted to assess the association of demographical features, Persian temperament, and psychological characteristics with the severity of COVID-19. Method: An online survey was sent to COVID-19 patients to collect their demographic information, COVID-19 symptoms, and clinical data. The Depression, Anxiety and Stress Scale (DAAS-21) questionnaire, Beck Depression Inventory (BDI-II), Spiel Berger State-Trait Anxiety Inventory (STAI) , Pittsburgh Sleep Quality Inventory (PSQI), and Persian general and brain temperament Questionnaire were also completed by 258 participants (127 men and 131 women) 45 days after recovery from COVID-19. Non-parametric analysis was used for statistical analysis. Results: Results showed the significant relationship of demographic factors such as weight, age and gender with the severity of the COVID-19 (P < 0.05). Mean scores of brain temperament (warm/cold) in the severe group were significantly lower than the moderate and mild groups (P < 0.05). There was a significant increase in the dry/wet temperament of the brain in the severe and moderate groups compared to the mild group (P < 0.05). The results of DASS-21 showed a significantly higher anxiety in patients with severe COVID-19 compared with moderate and mild groups (P < 0.05). The severe group was found to be significantly different compared to moderate group in the results of BDI-II (P < 0.05). The result of STAI (state and trait) showed a significant difference between the severe group and the mild and moderate groups. The score of PSQI between the moderate and mild groups was significant (P < 0.05). Conclusion: These results indicate the relationship between demographic factors such as weight, age and gender, brain temperament, as well as some psychological factors such as sleep quality and anxiety with the severity of the COVID-19 disease.

Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial.

OBJECTIVES: Saffron (Crocus sativus L.) has been widely used in traditional medicine as a treatment of nervous disorders. Saffron as an antioxidant can be considered effective for treatment of oxidative stress in ischemia stroke. Therefore, the aim of the present study was to investigate the role of aqueous extract of saffron in reducing oxidative stress in ischemic strokes patients. METHODS: Forty patients with acute ischemic stroke were randomly divided into two groups including control group and saffron group. During 4 days of experiment, control group received routine stroke care and saffron group received routine care plus capsule of saffron 400 mg/day (200 mg twice per day). Then, two groups were compared using the National Institute of Health Stoke Scale (NIHSS) and serum oxidative stress biomarkers, at the time of hospital admission and 4 days later as well. RESULTS: On the fourth day after ischemic stroke onset, antioxidant enzymes activities and glutathione (GSH) and total antioxidant capacity (TAC) levels were higher in the saffron group compared to the control group, while malondialdehyde (MDA) level was lower. In addition, the severity of stroke, based on the NIHSS scores, was significantly reduced after 4 days in the saffron group. The severity of stroke was negatively correlated with the levels of GSH and TAC and positively correlated with MDA level. CONCLUSIONS: Saffron has modulatory effects on ischemic-induced oxidative stress due to its free radical scavenging and antioxidant properties. Thus, saffron extract can be considered as a potential candidate therapy of the ischemic brain.

New Ways to Manage Pandemics: Using Technologies in the Era of COVID-19: A Narrative Review.

Objective: Health care systems and professionals worldwide are relying on technology as an essential partner to manage the COVID-19 epidemic. This paper explains how digital technologies can benefit the public, medical workers, and health care systems. Method: This nonsystematic literature review was conducted on different technologies and their impact and applications in the COVID-19 epidemic using proper search keywords on the PubMed, Google Scholar, and Science Direct databases. Results: We found various helpful technologies, which can help us to appropriately contain and manage the COVID-19 pandemic through broad areas of clinical care, logistics, maintenance of socioeconomic activities, and inspection. However, main challenges still need to be addressed for obtaining the full capacities of the technologies to support health care systems. Conclusion: Technologies can offer many innovative ideas and solutions against global and local emergencies. In this time of great vagueness and danger, we require all the resources we can collect to rescue ourselves and our patients. Barriers and challenges, such as lack of technology proficiency, confidentiality requirements, and reimbursement matters, need to be recognized and resolved rapidly, accurately, and compassionately.

Effects of transcranial direct current stimulation of prefrontal cortex on risk-taking behavior.

AIM: Recent cognitive neuroscience research shows that noninvasive brain stimulation can modify a wide range of behaviors in healthy people. Such regulation effects on human behaviors provide new insights into the neurobiology of cognitive processes and establish causal brain-behavior relations. Here, we aimed to examine the effects of transcranial electrical stimulation (TES) of the prefrontal cortex on risk-taking. METHODS: We performed a systematic search on the PubMed, Web of Science, and Cochrane databases with appropriate keywords for original studies reporting the use of TES to modulate risk-taking behavior in healthy individuals. Then, in the meta-analysis phase, a random-effects model was used to measure the pooled effect size (ES). RESULTS: Twenty articles were evaluated as eligible studies, including 16 articles on transcranial direct current stimulation (tDCS), two on transcranial alternating current stimulation, one on transcranial pulsed current stimulation, and one on high-definition tDCS. A meta-analysis showed a pooled estimated standardized ES of -0.20 (95% confidence interval [CI], -0.39 to -0.01), which indicates a small ES for active tDCS over the dorsolateral prefrontal cortex (DLPFC) in comparison to sham stimulation (z = 2.31, P = 0.03) in terms of less risky behaviors. Subgroup analysis showed that there is no significant ES for bilateral DLPFC stimulation (d = -0.01; 95%CI, -0.28 to 0.26), but a significant near-medium ES for unilateral DLPFC stimulation (d = -0.41; 95%CI, -0.71 to -0.10). CONCLUSION: Our findings support a significant impact of neuroregulation of the DLPFC on risk-taking behavior in healthy individuals. Unilateral noninvasive electrical stimulation of the DLPFC can result in a conservative risk-averse response style, probably through modulating plasticity of the relevant brain networks, including cortical and subcortical structures, as well as increasing subcortical dopaminergic activity.

The Effect of Prostration (Sajdah) on the Prefrontal Brain Activity: A Pilot Study.

INTRODUCTION: "Sajdah", a prostration position, is part of Muslim daily prayers. It seems to have several effects on the brain and heart function. This study aimed to investigate the prefrontal brain activity after 10 seconds of Sajdah in the direction of Qibla (the direction that a Muslim prays) while putting the forehead on the ground. METHODS: Three women and two men participated in this pilot study. Linear (absolute and relative power of θ (4-8Hz), α 1 (8-10 Hz), α 2 (10-12 Hz), ß 1 (12-16 Hz), ß 2 (16-20 Hz), ß 3 (20-30 Hz), γ 1 (30-40 Hz), γ 2 (40-50 Hz) and non-linear features (approximate entropy, Katz fractal dimension, Petrosian fractal dimension, spectral entropy, and sample entropy) from Fps channel were calculated. RESULTS: The relative ß to γ band, approximate and sample entropy, Petrosian fractal dimension and mean of amplitude decreased in open eye state in women. While θ to γ bands in the closed eye state decreased after Sajdah in women. The absolute γ bands in closed eye state and relative ß band in open eye state increased after Sajdah in men. CONCLUSION: The pilot study showed that 10 seconds of Sajdah has effects on brain activity and sometimes showed the opposite effect on genders.

Saffron (Crocus sativus) aqueous extract reverses the hypothalamus-pituitary-adrenal axis activity in rat model of post-traumatic stress disorder

Abstract Crocus sativus L., Iridaceae, has been used worldwide in traditional medicinefor treatment ofsome neurological disorderssuch as depression. Post-traumatic stress disorder is a mental disorder developed in peoplewho experience stressful events. Since stress has been proposed tocause thehypothalamic-pituitary-adrenal axis malfunction in post-traumatic stress disorder patients, this study aimed at investigating the effect of saffron aqueous extract on hypothalamic-pituitary-adrenal axis activity in rats of post-traumatic stress disorder model. Here, Post-traumatic stress disorder animals received an acute electro foot shock; however, 5 min before the stress session, these animals received an intra-cerebral-ventricular (10 µg/rat) infusion of either saffron aqueous extract or saline. Twenty one days later, they were re-exposedto the stress box withoutinducing stress, andthen were examined for their freezing behavior. The impact of stress and saffron aqueous extract on serum corticosterone, corticotrophin releasing hormone gene expression in hypothalamus and glucocorticoid receptor gene expression in pituitary gland werethen evaluated on day 28. Intra-cerebral-ventricular injection of saffron aqueous extract resulted in an increase in serum corticosterone level and reduced symptoms of freezing behavior, and corticotrophin releasing hormone and glucocorticoid receptor gene expression in post-traumatic stress disorder groups.Saffron administration could improve the symptoms of stress-induced post-traumatic stress disorder, possiblythrough the adjustment ofhypothalamic-pituitary-adrenal axis function.

Protective properties of the aqueous extract of saffron (Crocus sativus L.) in ischemic stroke, randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocus sativus L. has been used throughout the world in traditional medicine as a treatment for neurological disorders such as depression. Growing attention is currently being paid to the use of neuroprotective agents in ischemic strokes. AIM OF THE STUDY: This study assed the effect of saffron as a neuroprotective natural product in cerebral ischemia in human. STUDY DESIGN: Patients with acute ischemic stroke were randomly allocated to receive either routine stroke care (control group, n = 20) or routine care plus aqueous extract of saffron capsule (200 mg/day) (saffron-treated group, n = 19). Both groups were monitored during their four-day hospital stay and the three-month follow-up period. The groups were compared in terms of short- and long-term effects of saffron capsules using the National Institute of Health Stoke Scale (NIHSS), Barthel Scale, and serum neuron specific enolase (NSE), Brain-derived neurotrophic factor (BDNF), S100 levels. RESULTS: Based on the NIHSS, the severity of stroke during the first four days was significantly lower in the saffron-treated group than in the control group (P < 0.05). Compared to the levels on the first day, serum NSE and s100 levels were significantly decreased and BDNF concentration was increased in the saffron-treated group on the fourth day. Also, our results showed there was a negative significant non-linear cubic regression between BDNF concentration and score of NIHSS. At the end of the three-month follow-up period, the mean Barthel index was significantly higher in the saffron-treated group than in the control group (P < 0.001). CONCLUSION: The results of this study confirmed the short and long-term neuroprotective effects of aqueous extract of saffron on ischemic stroke in humans.

Ventral tegmental area inactivation alters hormonal, metabolic, and locomotor responses to inescapable stress.

Context: The involvement of unilateral and bilateral inhibition of the ventral tegmental area (VTA) in response to stress is not well understood. Objective: In the present study, the effect of unilateral and bilateral inhibition of the VTA on hormonal, metabolic, and locomotor responses to stress was assessed. Material and methods: Male rats seven days after cannulation into the VTA received electro foot-shock stress for seven consecutive days. Twenty minutes before induction of stress, 2% lidocaine hydrochloride or sterile saline (control) was injected either uni- or bi-laterally into the VTA. Results: Results showed that stress significantly increased serum corticosterone level, adrenal gland weight and anorexia, reduced weight gain, food-intake, and locomotor activity. However, bilateral inactivation of VTA prevented stress-induced these parameters changes. Conclusion: The present study demonstrated that the bilateral VTA blockade effectively relieves the symptoms of stress, while the unilateral VTA blockade does not significantly improve the changes caused by stress.

Bone marrow-derived mesenchymal stem cell and simvastatin treatment leads to improved functional recovery and modified c-Fos expression levels in the brain following ischemic stroke.

OBJECTIVES: The beneficial outcomes of bone marrow-derived mesenchymal stem cell (BMSC) treatment on functional recovery following stroke has been well established. Furthermore, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have also been shown to increase neuronal survival and promote the movement of BMSCs towards the sites of inflammation. However, the precise mechanisms mediating the improved neurological functional recovery in stoke models following a combination treatment of Simvastatin and BMSCs still remained poorly understood. MATERIALS AND METHODS: Here, an embolic stroke model was used to experimentally induce a focal ischemic brain injury by inserting a preformed clot into the middle cerebral artery (MCA). Following stroke, animals were treated either with an intraperitoneal injection of Simvastatin, an intravenous injection of 3 ×106 BMSCs, or a combination of these two treatments. RESULTS: Seven days after ischemia, the combination of Simvastatin and BMSCs led to a significant increase in BMSC relocation, endogenous neurogenesis, arteriogenesis and astrocyte activation while also reducing neuronal damage when compared to BMSC treatment alone (P<0.001 for all). In addition, based on western blot analysis, following stroke there was a significant decrease in c-Fos expression (P<0.001) in the combination treatment group. CONCLUSION: These results further demonstrate the synergistic benefits of a combination treatment and help to improve our understanding of the underlying mechanisms mediating this beneficial effect.

Aqueous extract of saffron administration along with amygdala deep brain stimulation promoted alleviation of symptoms in post-traumatic stress disorder (PTSD) in rats.

OBJECTIVE: Post-traumatic stress disorder (PTSD) as one of the most devastating kinds of anxiety disorders, is the consequence of a traumatic event. Crocus sativus L., commonly known as saffron have been traditionally used for treatment of stress and anxiety. In this study, we evaluated the effects of peripheral administration of saffron, along with deep brain stimulation (DBS) in a post-traumatic stress disorder (PTSD) model caused by contextual fear conditioning (electrical foot shock chamber) in male Wistar rats. MATERIALS AND METHODS: rats (220-250 g) were divided into 7 groups (n=8) and underwent stereotactic surgery for implantation of the electrodes in the right-baso lateral of the amygdala (BLA). After 7 days, some animals received the foot shock, followed by another 7-day treatment (DBS treatment or combination treatment by saffron 5 mg/kg (i.p)) then freezing behavior as a predicted response in the absence of the foot shock (re-exposure time) and general anxiety were measured using elevated plus maze test. Serum corticosterone level and amygdala c-Fos protein expression were assessed using ELISA and Western blot analysis, respectively. RESULTS: DBS treatment and the combination therapy of saffron (5 mg/kg (I.P)) with DBS significantly (p<0.001) increased serum corticosterone levels. Also both treatments could significantly (p<0.001) reduce c-Fos protein expression and freezing behaviors time. However, DBS treatment had no effect on the general anxiety in rats with PTSD. On the other hand, combination therapy significantly (p<0.001) reduced anxiety behavior in rats with PTSD. CONCLUSION: These results might show the potential of this combination therapy for treatment of treatment-resistant PTSD patients.

Crocin improved amyloid beta induced long-term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats.

Extracellular beta-amyloid (Aß) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aß models of the AD. The Aß peptide (1-42) was bilaterally administered into the frontal-cortex using stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improves spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aß-group. Passive avoidance test revealed that crocin significantly increased the step-through-latency compared to Aß-treated alone. These learning deficits in Aß-treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aß. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c-Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL-positive cells in the CA1 region and decreased c-Fos in the hippocampus compared to Aß-group. In vivo Aß treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirmed a neuroprotective action against Aß toxicity.

The Psychoactive Agent Crocin Can Regulate Hypothalamic-Pituitary-Adrenal Axis Activity.

Post-traumatic stress disorder (PTSD) occurs following life-threatening events. The activity of the hypothalamic-pituitary-adrenal (HPA) axis, which serves as the first line of defense against stress, is dysfunctional in this disorder. The current study aimed to investigate the role of Crocin in normalizing HPA function in an animal model of PTSD induced by electric foot shock. Rats were treated with Crocin 5 min prior to stress induction. The stimulus was re-introduced after 21 days, and we measured individual behaviors such as sniffing, rearing, grooming, and freezing. Enzyme-linked immunosorbent assays were performed to measure plasma levels of Corticosterone. On day 28, after rats were weighed and sacrificed, the adrenal and thymus glands were removed and subjected to real-time polymerase chain reaction to quantify the gene expression of corticotrophin-releasing hormone (CRH), glucocorticoid receptor (GluR), and arginine vasopressin (AVP). Our results demonstrate that rats re-exposed to a stressor developed characteristic symptoms of PTSD, but these were attenuated by Crocin. Treated rats showed significant changes in CRH expression in the hypothalamus, GluR expression in the pituitary, plasma Corticosterone levels, and freezing behavior. Together, these findings suggest that Crocin can regulate HPA axis activity in PTSD. It may serve an appropriate treatment for subjects who experience a traumatic event.

Characterization of Lung Fibroblasts More than Two Decades after Mustard Gas Exposure.

PURPOSE: In patients with short-term exposure to the sulfur mustard gas, the delayed cellular effects on lungs have not been well understood yet. The lung pathology shows a dominant feature consistent with obliterative bronchiolitis, in which fibroblasts play a central role. This study aims to characterize alterations to lung fibroblasts, at the cellular level, in patients with delayed respiratory complications after short-term exposure to the sulfur mustard gas. METHODS: Fibroblasts were isolated from the transbronchial biopsies of patients with documented history of exposure to single high-dose sulfur mustard during 1985-7 and compared with the fibroblasts of control subjects. RESULTS: Compared with controls, patients' fibroblasts were thinner and shorter, and showed a higher population doubling level, migration capacity and number of filopodia. Sulfur mustard decreased the in vitro viability of fibroblasts and increased their sensitivity to induction of apoptosis, but did not change the rate of spontaneous apoptosis. In addition, higher expression of alpha smooth muscle actin showed that the lung's microenvironment in these patients is permissive for myofibroblastic differentiation. CONCLUSIONS: These findings suggest that in patients under the study, the delayed pulmonary complications of sulfur mustard should be considered as a unique pathology, which might need a specific management by manipulation of cellular components.