The Effect of Spironolactone on ß-amyloid-Induced Memory Impairment in Male Rats: The Role of Microglial Inhibition.

Purpose: Neuroinflammation was indicated in the pathophysiology of Alzheimer's disease (AD). Previous reports have also signified that spironolactone has anti-inflammatory effects. Therefore, the aim of this study was to assess the modulatory effects of spironolactone on neuroinflammation and memory loss in a rat model of AD. Methods: The ß-amyloid protein fragment 25-35 (Aß) was injected in the dorsal hippocampus (5 µg/2.5 µL each side) of male Sprague-Dawley rats for four consecutive days to induce memory impairment. Animals have intraperitoneally received spironolactone (10, 25, or 50 mg/kg, N = 6/ group) or vehicle for 14 days. The passive inhibitory avoidance and the novel recognition tests were used for memory evaluation. Neuroinflammation was assessed by measuring the level of Iba1 protein, a marker of microglial activation, using western immunoblotting. Results: Different doses of spironolactone showed no significant changes in latency times and discriminations ratios in passive inhibitory avoidance and novel recognition tests, respectively, as compared to vehicle. However, spironolactone-treated groups showed significantly lower Iba1 protein levels in comparison to the vehicle-treated group (P < 0.01). Conclusion: Spironolactone had a modulatory effect on neuroinflammation through a repressive effect on microglial activation with no valuable effect on memory improvement in a rat model of AD. The findings of this study suggest that Aß-induced memory loss may not be directly linked to microglial activation. Spironolactone may be a potential candidate to be examined in other neuroinflammatory disorders.

The bidirectional effect of prelimbic 5-hydroxytryptamine type-4 (5-HT4) receptors on ACPA-mediated aversive memory impairment in adult male Sprague-Dawley rats.

OBJECTIVES: This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB1 cannabinoid receptor agonist) in the pre-limbic (PL) cortex. MATERIALS AND METHODS: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of 0.6 µl/rat into the PL area (0.3 µl per side). RESULTS: The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and ACPA on consolidation of aversive memory. RS67333 hydrochloride (0.5 µg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of 0.005 µg/rat with ineffective (0.001 µg/rat) or effective (0.1 µg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS67333 had a bidirectional effect on ACPA-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0.005, 0.01, 0.1, or 0.5 µg/rat); but its concomitant use with an effective dose of ACPA (0.1 µg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity. CONCLUSION: This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the 5-HT4 serotonergic receptors.

Insulin-Like Growth Factor 2 (IGF-2) Regulates Neuronal Density and IGF-2 Distribution Following Hippocampal Intracerebral Hemorrhage.

BACKGROUND: The insulin-like growth factor 2 (IGF-2) is a growth factor and anti-inflammatory cytokine that plays a crucial role in memory consolidation. However, the precise role of this factor in acute brain damage is still unclear. The present study aimed to evaluate the variations in hippocampal IGF-2 distribution on different days and investigate the effect of recombinant IGF-2 on memory cell density, and IGF-2 distribution following acute hippocampal damage resulting from intracerebral hemorrhage (ICH). METHODS: ICH was induced by injection of 100 µL of autologous blood into the left hippocampus of 72 male Sprague-Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 min post-induction of ICH in the ICH-IGF-2 group. Then, on postoperative days 1, 3, 7, and 14, samples of brain tissue were collected to perform histopathological and immunohistochemical examinations. RESULTS: The stereological study indicated that the volume of the hippocampus and the number of neurons had a significant reduction, and the infarct volume had a significant increase following ICH. Following the injection of IGF-2, a significant improvement was observed in stereological studies. Immunohistochemical data showed that IGF-2 distribution increased in the hippocampus on different days after ICH, and IGF-2 injection led to a dramatic reduction in this distribution. CONCLUSIONS: In summary, the gradual increase of endogenous IGF-2 as growth and anti-inflammatory factor following hemorrhagic stroke reveals a critical role of this factor in brain recovery after injury. Moreover, the injection of IGF-2 can prevent cell death and alleviate the damage caused by the hemorrhagic stroke.

The effect of Salvia officinalis extract on symptoms of flushing, night sweat, sleep disorders, and score of forgetfulness in postmenopausal women.

BACKGROUND: Complications of hormone therapy (as replacement) during menopause prompted us to research on alternative therapies including herbal therapy in this regard. OBJECTIVES: The effect of Salvia officinalis extract on symptoms of flushing, night sweat, sleep disorders, and score of forgetfulness in postmenopausal women on Namazi Hospital Bone Density Center in Shiraz 2015. METHODS: In a double-blind randomized controlled clinical trial, 66 postmenopausal women complaining of menopausal symptoms were divided into two groups of intervention and control, respectively. The intervention group received S. officinalis tablets (containing 100 mg S. officinalis extract), with a dose of three tablets a day for 3 months, while the control group received placebo tablets with the same prescription order. MRS (Menopause Rating Scale) and PSQI (Pittsburgh Sleep Quality Index) questionnaires were completed at the beginning and end of the study. The checklists of hot flushing and night sweating were completed a week before the intervention and at weeks 2, 4, 6, 8, 10, 12 during the intervention. Finally, the data were analyzed through SPSS18 software, using paired t-test, ANOVA. A significant level of 5% was considered. RESULTS: According to the paired t-test, the mean score of flushing, palpitation, sleeping disorders, muscle and joint aches, depression, nervousness, anxiety, and sexual desire and satisfaction significantly decreased by 1.6, 0.4, 1.6, 2.1, 1.4, 1.2, 1.6, and 0.8 units, respectively, in the intervention group compared to the control group (P < 0.001). Therefore, the mean score of PSQI significantly decreased by 3.8 units in the intervention group after the intervention (9.4 ± 3.7 vs 5.6 ± 1.9 (P < 0.05). CONCLUSIONS: Salvia extract improved menopausal symptoms such as flushing, night sweat, heart palpitations, muscle and joint pain, depression, anxiety, sleep disorders, and sexual desire.

Interaction of sigma-1 receptor modulators with seizure development in pentylenetetrazole-induced kindled mice.

This study aimed to investigate the effects of sigma receptor modulators, opipramol and BD-1063, on epileptogenesis in pentylenetetrazole (PTZ)-kindling model of epilepsy. Mice (n = 6/group) were received PTZ (30 mg/kg), PTZ plus opipramol (5 or 10 mg/kg), PTZ plus opipramol (5 mg/kg) plus BD-1063 (5 mg/kg, a selective sigma-1 receptor antagonist), and PTZ plus BD-1063 on alternate days for 15 days. Opipramol (5 and 10 mg/kg) + PTZ groups became fully kindled and had higher seizure scores compared to the PTZ group. In contrast, the PTZ plus BD-1063 and the PTZ plus opipramol (5 mg/kg) plus BD-1063 group did not show full kindling. These findings indicate that opipramol has a pro-convulsant effect, which is possibly mediated through activation of sigma-1 receptors.

The neuroprotective mechanism of cinnamaldehyde against amyloid-ß in neuronal SHSY5Y cell line: The role of N-methyl-D-aspartate, ryanodine, and adenosine receptors and glycogen synthase kinase-3ß.

OBJECTIVE: Cinnamaldehyde may be responsible for some health benefits of cinnamon such as its neuroprotective effects. We aimed to investigate the cinnamaldehyde neuroprotective effects against amyloid beta (Aß) in neuronal SHSY5Y cells and evaluate the contribution of N-methyl-D-aspartate (NMDA), ryanodine, and adenosine receptors and glycogen synthase kinase (GSK)-3ß, to its neuroprotective effects. MATERIALS AND METHODS: After seeding the cells in 96-well plates, adenosine (20, 40, 80, and 120 µM), NMDA (20, 40, 80, and 120 µM), and dantrolene (as a ryanodine receptor antagonist; 2, 4, 6, 8, and 16 µM) were added to the medium containing Aß25-35 and/or cinnamaldehyde. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide method was used to assess neurotoxicity and western blot to measure the GSK-3ß protein level. RESULTS: Cinnamaldehyde (15, 20, 23, and 25 µM) significantly reversed Aß-induced toxicity in SHSY5Y neuronal cells. Adenosine (20, 40, 80 and 120 µM) inhibited the neuroprotective effects of cinnamaldehyde (15 µM). NMDA (20, 40, 80, and 120 µM) reduced cinnamaldehyde (15 and 23 µM) neuroprotective effects against Aß neurotoxicity. Dantrolene (2, 4, 8, and 16 µM) significantly reduced cinnamaldehyde (15 µM) neuroprotective effects. Cinnamaldehyde (15 and 23 µM) suppressed the Aß-induced increment of GSK-3ß protein level. CONCLUSION: NMDA and adenosine receptors suppression together with ryanodine receptors stimulation may be relevant to cinnamaldehyde neuroprotective effects against Aß neurotoxicity. Moreover, the inhibition of GSK-3ß may contribute to the cinnamaldehyde neuroprotection.

Validity and Reliability of the Persian Versions of National Institute of Health Stroke Scale and Modified National Institute of Health Stroke Scale in Hospitalized Patients.

BACKGROUND: National Institute of Health Stroke Scale (NIHSS) and Modified National Institute of Health Stroke Scale (mNIHSS) are two valid and reliable questionnaires that assess stroke severity. This study aimed to examine and compare the validity and reliability of Persian versions of NIHSS and mNIHSS in hospitalized patients. MATERIALS AND METHODS: The English versions of NIHSS and mNIHSS were translated to Persian (forward and backward), and three neurologists examined the face and content validity of both questionnaires. The Persian versions of NIHSS and mNIHSS were used in 75 hospitalized stroke patients (hemorrhagic and obstructive) admitted to Namazi teaching hospital, Shiraz, Iran. The reliability and validity of the Persian versions were examined by Cronbach's alpha coefficient and convergent validity. RESULTS: The values of Cronbach's alpha for Persian versions of NIHSS and mNIHSS were 0.81 and 0.86, respectively. The scaling success of convergent validity in NIHSS and mNIHSS were 80% and 100%, respectively. CONCLUSION: The Persian versions of NIHSS and mNIHSS were reliable and valid. However, mNIHSS was more valid and reliable than NIHSS. Persian version of mNIHSS can be suggested to be used for assessing stroke severity in hospitalized stroke patients by neurologists and researchers.

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice.

BACKGROUND: There is no universally accepted behavioral scoring to define the early development of pentylenetetrazole (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. MATERIALS AND METHODS: Twenty-four mice were intraperitoneally injected with a sub-convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. RESULTS: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub's tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. CONCLUSION: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub's tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling.

Curcumin Effects on Memory Impairment and Restoration of Irregular Neuronal Distribution in the Hippocampal CA1 Region After Global Cerebral Ischemia in Male Rats.

INTRODUCTION: Global Cerebral Ischemia (GCI) causes neuronal damage with subsequent neurological and cognitive impairments. Curcumin has anti-inflammatory, antioxidant, and neuroprotective properties, which makes it a potential candidate for improving GCI-induced impairments. This study aimed to investigate the effects of curcumin on the neurological and memory deficits, as well as spatial neuronal distribution in the Cornu Ammonis 1 region after GCI in rats. METHODS: 56 Sprague-Dawley male rats were randomly assigned into 4 groups of sham (n=14), control (n=14), curcumin 50 mg/kg (n=14), and curcumin 100 mg/kg (n=14). Each group was divided into the two subgroups of short-term (7 days) and long-term (28 days) treatment periods. The Neurological Severity Score (NSS), passive avoidance task, and the traction test were performed at postoperative days of 0, 1, 2, 3, 7, 14, 21, and 28. The novel object recognition test and Voronoi tessellation were carried out on days 7 and 28 after GCI. RESULTS: Curcumin 100 mg/kg significantly decreased neurological severity score on postoperative days of 7 and 28 compared with the control (P<0.001) and curcumin 50 mg/kg groups (P<0.05-P<0.001), respectively. Also, curcumin 100 mg/kg significantly increased step-through latency times on postoperative days of 3-28 and 14-28 compared with the control (P<0.05-P<0.001) and curcumin 50 mg/kg groups (P<0.01-P<0.001). Moreover, it increased the novelty preference index during the novel object recognition test in the 28-day treatment subgroup after GCI. Curcumin (100 mg/kg) could maintain the neuronal aggregation in the CA1 region after GCI at a level near to what is generally observed in normal rats. CONCLUSION: Curcumin could improve memory and neurological deficits and restore irregular neuronal distribution in the CA1 region after GCI in a time-dependent manner, and its higher dose was more effective than its lower dose. Curcumin may have beneficial effects on reducing brain complications after ischemia.

Quercus Brantii Lindl. Vaginal Douche Versus Clotrimazole on Vaginal Candidiasis: A Randomized Clinical Trial.

OBJECTIVES: Vaginal Candidiasis with an approximate prevalence of 30% is the second cause of vaginal infections. Antifungal azole is the first treatment for Vaginal Candidiasis; however, some side effects have been reported for this chemical medicine. Based on the antifungal activity of Inner Stratum of Quercus Brantii (Q. Brantii), the aim of our study was to compare the effects of vaginal douche of Q. Brantii extract and clotrimazole on vaginal candidiasis symptoms before and after the treatments, in women. METHODS: 89 non-pregnant women with positive KOH test which is capable of identifying the presence of hyphae and mycelium by adding KOH (10%), and a positive vaginal candidiasis culture were randomly divided into two experimental groups, using permuted block randomization method. One group received clotrimazole vaginal cream (1%) and the other group received vaginal douche of Q. Brantii extract. Groups were treated for 7 days and KOH tests and cultures were evaluated again. Data were analyzed via chi-square and independent t-test, using SPSS software. RESULTS: According to the results, there were no significant differences between experimental groups for demographic characteristics like age (p=0.403), BMI (p=0.911), educational levels (p=0.862) and contraceptive methods (p=0.702). Moreover, significant differences were seen in vaginal discharge between the groups after the treatments (P=0.043). CONCLUSION: The results suggested that the therapeutic effect of vaginal douche of Q. Brantii extract was approximately similar to that of clotrimazole vaginal cream.

Effect of chamomile capsule on lipid- and hormonal-related parameters among women of reproductive age with polycystic ovary syndrome.

BACKGROUND: According to traditional herbal medicine, chamomile has been considered as one of the herbal remedies for patients with polycystic ovary syndrome (PCOS). The study aimed to investigate the effect of chamomile on lipid and hormonal parameters in women of reproductive age with PCOS. MATERIALS AND METHODS: This study is a randomized clinical trial which was conducted on 80 women (40 patients in each group) of childbearing age with PCO. The intervention group received 370 mg oral capsules of chamomile three times a day for 3 months. The control group did receive starch capsule (three times a day). Hormonal and lipid parameters were examined before and 3 months after the intervention. RESULTS: The mean age of the patients was 22.40 ± 5.10 and 24.38 ± 6.14 years in the intervention and control groups, respectively. Decreased level of testosterone was observed in the intervention group (in women with PCOS) who received chamomile capsules (P = 0.017). A significant difference was not seen in low-density lipoprotein cholesterol level (P = 0.249), high-density lipoprotein cholesterol (P = 0.073), triglycerides (P = 0.603), the hormone dehydroepiandrosterone sulfate (P = 0.423), and the ratio of luteinizing hormone/follicle-stimulating hormone (LH/FSH) in the experimental and control groups after the intervention (P = 0.420). CONCLUSION: According to the findings, oral administration of chamomile capsule caused a significant decrease in total testosterone levels in these patients. However, no significant change was reported with lipid parameters, the ratio of LH/FSH, and dehydroepiandrosterone sulfate level.

Evaluation of aromatherapy with essential oils of Rosa damascena for the management of premenstrual syndrome.

OBJECTIVE: To investigate the efficacy of aromatherapy with essential oils of Rosa damascena for the management of premenstrual syndrome (PMS). METHODS: The present triple-blind randomized clinical trial was conducted between March 5, 2016, and February 20, 2017, among female students attending Shiraz University of Medical Sciences, Shiraz, Iran, who experienced PMS, had a menstrual cycle of 24-35 days, were not using vitamin supplements or hormonal drugs, and did not have any underlying diseases. Block randomization was used to assign participants to an intervention group receiving aromatherapy with R. damascena at a 4% concentration or a control group who received aromatherapy with 100% sweet almond oil. Aromatherapy was performed for 5 minutes, twice daily, for a total of 5 days during the luteal phase. The premenstrual symptoms screening tool questionnaire was completed at baseline and after 1 and 2 months of treatment. Per-protocol analyses were performed with patients and investigators masked to group assignments. RESULTS: There were 66 participants enrolled and 64 completed the study (33 in the intervention group and 31 in the control group). At 2 months, aromatherapy with R. damascena was associated with improved psychological (P<0.001), physical (P<0.001), social (P=0.002), and total (P<0.001) PMS symptoms compared with baseline. By contrast, no improvements were recorded in the control group. CONCLUSION: Aromatherapy with R. damascena improved multiple symptoms of PMS. IRANIAN REGISTRY OF CLINICAL TRIALS: IRCT2016031113940N3.

The effect of melatonin on the lipid levels in menopausal women: A double-blind, controlled, clinical trial.

BACKGROUND: Cardiovascular diseases are the major public health problem in many countries and are responsible for more than half of the deaths in above 50-year-old women. The most common curable risk factor of these disorders is hypoestrogenemia resulting from menopause. The present study aimed to investigate the effect of melatonin on plasma lipid levels in menopausal women. MATERIALS AND METHODS: The present double-blind, placebo-controlled, clinical trial was conducted in 2013-2014 on 240 menopausal women between 40 and 60 years old referring to the Gynecology and obstetrics clinics of Shiraz University of Medical Sciences who were randomly divided into two groups. The intervention group received 3 mg melatonin tablets and the control group received the placebo for 3 months. The data were gathered using the demographic information questionnaire and lipid profile test before and 3 months after the intervention. Then, the data were analyzed through the SPSS statistical software (version 16). The repeated measures analysis of variance, the least significant difference, the independent-sample t, the Chi-square, and Fisher's exact tests were done for data analysis. RESULTS: The two study groups were similar regarding the demographic and clinical variables at the beginning of the study. In the melatonin group, the amount of triglyceride increased from 140.34 ± 48.29 before the study to 151.24 ± 54.60 3 months after the intervention and no significant difference was observed between the two groups in this regard (confidence interval [CI] = 95%, P > 0.05). In addition, no significant difference was found between the two groups concerning low-density lipoprotein cholesterol level (CI = 95%, P = 0.125). CONCLUSION: Melatonin was not effective in reduction of lipid levels. However, further controlled studies are needed to be conducted on the issue.

Effect of Recombinant Insulin-like Growth Factor-2 Injected into the Hippocampus on Memory Impairment Following Hippocampal Intracerebral Hemorrhage in Rats.

BACKGROUND: Insulin-like growth factor 2 (IGF-2) is a growth factor and an anti-inflammatory cytokine that plays a pivotal role in memory. In this study, we examined the effect of recombinant IGF-2 on memory impairment due to intracerebral hemorrhage (ICH). Avoidance and recognition memory, locomotor activity, neurological deficit score (NDS), and the level of the IGF-2 gene expression were evaluated. MATERIALS AND METHODS: To induce ICH, 100 µL of autologous blood was injected into the left hippocampus of male Sprague Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 minutes after the induction of ICH. Then, over two weeks, NDS, locomotor activity, passive avoidance, and novel object recognition (NOR) test were evaluated. Finally, the level of IGF-2 gene expression was evaluated by using the real-time polymerase chain reaction technique. RESULT: Our results indicated that recombinant IGF-2 injection significantly increased step-through latency (P<0.001) and total time spent in the dark box (P<0.01). However, no significant difference was seen in recognition memory and NDS. Locomotor activity did not significantly change in any group. A significantly reduced level of IGF-2 was observed after two weeks (P<0.05). CONCLUSION: The results of this study show that a single dose of recombinant IGF-2 injection can influence hippocampus-dependent memories. Importantly, IGF-2 did not change locomotor activity and NDS after two weeks, which probably represents its specific function in memory.

Topical Olive Leaf Extract Improves Healing of Oral Mucositis in Golden Hamsters.

STATEMENT OF THE PROBLEM: Oral mucositis (OM) is a common side effect of anti-cancer drugs and needs significant attention for its prevention. PURPOSE: This study aimed to evaluate the healing effects of olive leaf extract on 5-fluorouracil-induced OM in golden hamster. MATERIALS AND METHOD: OM was induced in 63 male golden hamsters by the combination of 5-fluorouracil injections (days 0, 5 and 10) and the abrasion of the cheek pouch (days 3 and 4). On day 12, hamsters were received topical olive leaf extract ointment, base of ointment, or no treatment (control) for 5 days. Histopathology evaluations, blood examinations, and tissue malondialdehyde level measurement were performed 1, 3 and 5 days after treatments. RESULTS: Histopathology score and tissue malondialdehyde level were significantly lower in olive leaf extract treated group in comparison with control and base groups (p= 0.000). Significant decreases in white blood cell, hemoglobin, hematocrit , and mean corpuscular volume and an increase in mean corpuscular hemoglobin concentration were observed in olive leaf extract treated group in comparison with control and base groups (p< 0.05). CONCLUSION: Our findings demonstrated that daily application of olive leaf extract ointment had healing effect on 5-fluorouracil induced OM in hamsters. Moreover, the beneficial effect of olive leaf extract on OM might be due to its antioxidant and anti-inflammatory properties.

Anticonvulsant Effect of the Aqueous Extract and Essential Oil of Carum Carvi L. Seeds in a Pentylenetetrazol Model of Seizure in Mice.

BACKGROUND: Carum carvi L. (caraway), known as black zeera in Iran, has been indicated for the treatment of epilepsy in Iranian folk medicine. This study evaluated whether the aqueous extract and essential oil of caraway seeds have anticonvulsant effects in mice. METHODS: The anticonvulsant effects of the aqueous extract (200, 400, 800, 1600, and 3200 mg/kg, i.p.) and essential oil (25, 50, 100, 200, and 400 mg/kg, i.p.) of caraway were assessed using pentylenetetrazol (PTZ; 95 mg/kg i.p.) induced convulsions. Diazepam (3 mg/kg) was used as positive control. The latency time before the onset of myoclonic, clonic, and tonic convulsions and the percentage of mortality were recorded. In addition, the effect of caraway on neuromuscular coordination was evaluated using the rotarod performance test. RESULTS: The extract and essential oil dose-dependently increased the latency time to the onset of myoclonic (ED50, 1257 and 62.2 mg/kg, respectively) and clonic (ED50, 929 and 42.3 mg/kg, respectively) seizures. The extract and essential oil of caraway prevented the animals from tonic seizure with ED50s of 2142.4 and 97.6 mg/kg, respectively. The extract and essential oil of caraway protected 28.6 and 71.4% of the animals from PTZ-induced death, respectively, and had no significant effect on neuromuscular coordination. CONCLUSION: This study showed that the aqueous extract and essential oil of caraway had anticonvulsant properties. However, the essential oil was more potent and effective than was the aqueous extract as an anticonvulsant. Additionally, the anticonvulsant effect of caraway was not due to a muscle relaxant activity. These findings support the acclaimed antiepileptic effect of caraway in folk medicine and propose its potential use in petit mal seizure in humans.

Effect of Melissa officinalis Capsule on the Intensity of Premenstrual Syndrome Symptoms in High School Girl Students.

BACKGROUND: Several studies are conducted on Premenstrual Syndrome (PMS). However, a few herbal surveys exist on the treatment of PMS in Iran. Due to the sedative effects of Melissa officinalis (M. officinalis), this question comes to mind that "can it be used in the treatment of PMS symptoms?" OBJECTIVES: The current study aimed to assess the effect of M. officinalis capsule on the intensity of PMS in high-school girls. MATERIALS AND METHODS: A double-blind randomized, placebo-controlled trial was performed on 100 high school girls from 2013 to 2014. The intervention group (n = 50) received 1200 mg of M. officinalis essence daily from the first to the last day of their menstrual cycle for three consecutive cycles. The second group (n = 50) received the placebo. The premenstrual symptoms screening tool was used to assess the intensity of PMS symptoms in the two groups before and one, two, and three months after the intervention. The data were analyzed using paired t-test and repeated measures analysis of variance. RESULTS: The results of repeated measures test revealed a significant reduction (P < 0.001) in PMS symptoms. Overall, the mean score of PMS intensity in the intervention group was 42.56 + 15.73 before the intervention and changed to 32.72 ± 13.24, 30.02 ± 12.08, and 13.90 ± 10.22 at the three consecutive months after the intervention, respectively (P = 0.001). CONCLUSIONS: M. officinalis capsules were effective in reduction of the PMS symptoms. Yet, application of this medication requires further investigations.

Acute and chronic effects of lithium on BDNF and GDNF mRNA and protein levels in rat primary neuronal, astroglial and neuroastroglia cultures.

OBJECTIVES: The neuroprotective effect of lithium has been attributed to its therapeutic action. However, the role of glial cells particularly astrocytes, and the possible interactions between neurons and astrocytes in neuroprotective effects of lithium have been disregarded. Thus, the aim of this study was to evaluate the direct effects of lithium on brain derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF) in rat primary neuronal, astrocytes, and mixed neuro-astroglial cultures to assess the possible effects of lithium on astrocytes and neuro-astroglia interactions. MATERIALS AND METHODS: Rat primary astrocyte, neuronal and mixed neuro-astrocyte cultures were prepared from cortices of 18-day embryos. Cell cultures were exposed to lithium (1 mM) or vehicle for 1 day (acute) or 7 days (chronic). BDNF and GDNF mRNA and protein levels were determined by RT-PCR and ELISA, respectively. RESULTS: Chronic but not acute lithium treatment increased intracellular BDNF and GDNF protein levels in rat primary neuronal and astrocyte cultures, respectively (P<0.05). However, chronic lithium treatment had no significant effect on intracellular BDNF protein level in astrocyte and mixed neuron-astrocyte cultures or GDNF protein levels in mixed neuron-astrocyte culture. Furthermore, acute and chronic lithium treatment had no significant effect on mRNA and extracellular BDNF and GDNF protein levels in three studied cultures. CONCLUSION: Present study showed that chronic lithium treatment affected neurotrophins both in neurons and astrocytes in a cell-type specific manner with no effect on neuron-astrocyte interactions. The findings of this study also highlighted the importance of astrocytes as drug targets involved in the neuroprotective action of lithium.

Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100ß in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM) or vehicle for 1day (acute) or 7 days (chronic). RT-PCR and ELISA determined S100ß mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100ß in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05). Acute and chronic lithium treatments exerted no significant effects on intracellular S100ß protein levels in astrocytes, and extracellular S100ß protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100ß mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

Acute and Chronic Effects of N-acetylcysteine on Pentylenetetrazole-induced Seizure and Neuromuscular Coordination in Mice.

BACKGROUND: N-acetylcysteine (NAC) has been indicated against experimental seizures, but with relatively inconclusive results. This study was undertaken to evaluate whether NAC exerts a dose-dependent anticonvulsant effect and to determine NAC safe therapeutic dose range and its muscle-relaxant activity in both acute and chronic uses. METHODS: Following intraperitoneal (i.p.) administration of N-acetylcysteine acutely (50-300 mg/kg) or chronically for 8 days (25-300 mg/kg), mice were injected with PTZ (90 mg/kg, i.p.) and latency times to the onset of myoclonic and clonic seizures and protection against death were recorded. Changes in body weight and mortality rate were considered as parameters for drug safety. The muscle-relaxant activity of NAC was assessed by rotarod test. RESULTS: Acute and chronic treatment with NAC delayed latency times to myoclonic and clonic seizures in a dose-dependent manner, but with no significant prevention against PTZ-induced death. Chronic administration of 300 mg/kg NAC was fully lethal while lower doses (100 and 150 mg/kg) resulted in a significant weight loss and decreased stay time on rotarod. Acute treatment with NAC had no significant effect on stay time on rotarod at all studied doses. CONCLUSION: NAC exerts a dose-dependent anticonvulsant effect in acute and chronic uses, with no muscle relaxant activity. NAC has higher efficacy in preventing seizure in chronic than acute treatment, but its chronic use at higher doses of 75 mg/kg may be associated with side effects and/or toxicity. These findings suggest that low doses of NAC may have a potential use as a prophylactic treatment for absence seizure in human.