Curcumin Lowers the Accelerated Speed of Epileptogenesis by Traumatic Brain Injury.

Background: Traumatic brain injury or TBI can underlie epilepsy. Prevention of PTE has been of great interest to scientists. Given the antiepileptic, antioxidant and anti-inflammatory activities of curcumin, we examined whether this compound can affect epileptogenesis in rats after TBI. Methods: Curcumin was injected once a day for two weeks. TBI was induced in the temporal cortex of anesthetized rats using a controlled cortical impact device. One day after TBI, pentylenetetrazole (PTZ), 35 mg/kg, was injected i.p. every other day until manifestation of generalized seizures. The number of PTZ injections was then recorded. Moreover, the extent of cortical and hippocampal IL-1ß and glial fibrillary acidic protein (GFAP) expression in the epileptic rats were measured by Western blot analysis. Results: Curcumin 50 and 150 mg/kg prevented the development of kindling, whereas TBI accelerated the rate of kindling. Curcumin 20 mg/kg prohibited kindling facilitation by TBI, and reduced the expression of IL-1ß and GFAP induced by TBI. Conclusion: Curcumin can stop the acceleration of epileptogenesis after TBI in rats. Inhibiting hippocampal and cortical overexpression of IL-1ß and GFAP seems to be involved in this activity.

High and Low-Frequency Stimulation Effect on Epileptiform Activity in Brain Slices.

Background: Neurostimulation is one of the new therapeutic approaches in patients with drug-resistant epilepsy, and despite its high efficiency, its mechanism of action is still unclear. On the one hand, electrical stimulation in the human brain is immoral; on the other hand, the creation of the epilepsy model in laboratory animals affects the entire brain network. As a result, one of the ways to achieve the neurostimulation mechanism is to use epileptiform activity models In vitro. In vitro models, by accessing the local network from the whole brain, we can understand the mechanisms of action of neurostimulation. Methods: A literature search using scientific databases including PubMed, Google Scholar, and Scopus, using "Neurostimulation" and "epileptiform activity" combined with "high-frequency stimulation", " low-frequency stimulation ", and "brain slices" as keywords were conducted, related concepts to the topic gathered and are used in this paper. Results: Electrical stimulation causes neuronal depolarization and the release of GABAA, which inhibits neuronal firing. Also, electrical stimulation inhibits the nervous tissue downstream of the stimulation site by preventing the passage of nervous activity from the upstream to the downstream of the axon. Conclusion: Neurostimulation techniques consisting of LFS and HFS have a potential role in treating epileptiform activity, with some studies having positive results. Further investigations with larger sample sizes and standardized outcome measures can be conducted to validate the results of previous studies.

Melittin ameliorates motor function and prevents autophagy-induced cell death and astrogliosis in rat models of cerebellar ataxia induced by 3-acetylpyridine.

BACKGROUND: Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. This study aims to investigate the therapeutic effects of melittin (MEL) on a 3-acetylpyridine-induced (3-AP) cerebellar ataxia (CA) rat model. METHODS: Initially, CA rat models were generated by 3-AP administration followed by the subcutaneous injection of MEL. The open-field test was used for the evaluation of locomotion and anxiety. Immunohistochemistry was also conducted for the autophagy markers of LC3 and Beclin1. In the next step, the morphology of the astrocyte, the cell responsible for maintaining homeostasis in the CNS, was evaluated by the Sholl analysis. RESULTS: The findings suggested that the administration of MEL in a 3-AP model of ataxia improved locomotion and anxiety (P < 0.001), decreased the expression of LC3 (P < 0.01) and Beclin1 (P < 0.05), increased astrocyte complexity (P < 0.05) and reduced astrocyte cell soma size (P < 0.001). CONCLUSIONS: Overall, the findings imply that the MEL attenuates the 3-AP-induced autophagy, causes cell death and improves motor function. As such, it could be used as a therapeutic procedure for CA due to its neuroprotective effects.

The plasma level of glutamic acid decarboxylase 65 (GAD65) increased in severely autistic Iranian children.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder. The major etiological mechanism lies in glutamatergic/GABAergic imbalance. The aim of this study was to evaluate the plasma levels of glutamic acid decarboxylase 65 (GAD65) protein in mildly and severely autistic patients, and also to compare plasma GAD65 concentration in mild and severe autism. METHOD: In total, 62 autistic patients (aged 6-9 years) and 17 age-matched neurotypically healthy controls were included in the study. The diagnosis, as well as the level of autism, was assessed by applying the Gilliam Autism Rating Scale. Plasma GAD65 protein level was determined using an enzyme-linked immunosorbent assay (ELISA) kit for GAD65. RESULTS: Our findings showed no remarkable alteration in plasma GAD65 concentration in patients with mild autism as compared to healthy subjects, while patients with severe autism showed an increased plasma level of GAD65 as compared to healthy controls and mildly autistic patients. CONCLUSION: Our findings suggest the level of plasma GAD65 to be considered a potential diagnostic biomarker for the severity of autism (Fig. 2, Ref. 40).

Alteration in Neuregulin 1/ERbB4 in Absence Epilepsy: Regulatory Effect on TRPV1 Expression.

Introduction: The footprint of Neuregulin 1 (NRG1) / ERbB4 in the pathophysiology of some neurological disorders and TRPV1 regulation has been indicated. The alterations in NRG1 and ErbB4 as well as the TRPV1 signaling pathway were investigated during the development of absence epilepsy in the genetic animal model of absence epilepsy. Methods: Male WAG/Rij and Wistar rats were divided into four experimental groups of two and six months of age. The protein levels of NRG1, ERbB4, and TRPV1 were measured in the somatosensory cortex and hippocampus. Results: The cortical protein levels of NRG1 and ErbB4 in the 6-month-old WAG/Rij rats were lower than in Wistar rats. Protein levels of TRPV1 were lower in two- and six-month-old WAG/Rij rats compared to age-matched Wistar rats.Hippocampal protein levels of NRG1 in 6-month-old WAG/Rij rats were lower than two-month-old WAG/Rij rats. Low levels of ErbB4 protein in two-month-old and high levels in six-month-old WAG/Rij rats were found compared to Wistar rats. Protein levels of TRPV1 were lower in the two-month-old and higher in the six-month-old WAG/Rij rats compared to age-matched Wistar rats.Furthermore, a high correlation between NRG1/ERbB4 and TRPV1 expressions in the cortex and hippocampus was indicated. The expression of NRG1/ERbB4 and TRPV1 followed a similar pattern during the life span of Wistar and WAG/Rij rats. Conclusion: Our findings indicated the potential role of the NRG1/ErbB4 pathway as well as TRPV1 in the pathogenesis of absence epilepsy. The regulatory effect of the ERbB4 receptor on the TRPV1 expression has been suggested following the similar pattern of expression.

Exercise Improved the Anti-Epileptic Effect of Carbamazepine through GABA Enhancement in Epileptic Rats.

Carbamazepine (CBZ) is an anticonvulsant drug that usually is used for the treatment of seizures. The anti-epileptic and the anti-epileptogenic effect of exercise has been reported, as well. This study was aimed to evaluate the synergic effect of combined therapy of exercise and CBZ in epileptic rats, as well as the alternation of the GABA pathway as a possible involved mechanism. The seizure was induced by pentylenetetrazol (PTZ) injection. Animals were divided into sham, seizure, exercise (EX), CBZ (25, 50 and 75), EX + CBZ (25, 50 and 75). Treadmill forced running for 30 min has been considered as the exercise 5 days per week for four weeks. CBZ was injected in doses of 25, 50 and 75 mg/kg, half an hour before seizure induction and 5 h after doing exercise in the animals forced to exercise. Seizure severity reduced and latency increased in the EX + CBZ (25) and EX + CBZ (50) groups compared to the seizure group. The distribution of GAD65 in both hippocampal CA1 and CA3 areas increased in the EX + CBZ (75) group. GABAA receptor α1 was up-regulated in the CA3 area of the EX + CBZ (75) group. The distribution of GAD65 in the cortical area increased in EX, EX + CBZ (50), CBZ (75) and EX + CBZ (75) groups. GABAA receptor α1 was up-regulated in the neocortex of EX + CBZ (50), CBZ (75) and EX + CBZ (75) groups. Our findings suggested that exercise has improved the efficacy of CBZ and reduced the anti-epileptic dose. The enhancement of GABA signaling might be involved in the synergistic effect of exercise and CBZ.

Olfactory mucosa stem cells delivery via nasal route: a simple way for the treatment of Parkinson disease.

Finding a simple and effective way for transferring cells to the brain lesion site with minimum side effects mounts a challenge in cell therapy. Cell delivery via nasal route using the bypassing the blood-brain barrier (BBB) property is a simple and non-invasive strategy without serious complications such as trauma. Therefore, it is a suitable technique to treat neurodegenerative disorders like Parkinson's disease (PD). Olfactory ectomesenchymal stem cells (OE-MSCs) located in the lamina propria of olfactory mucosa could be differentiated into dopaminergic neurons under in vitro and in vivo conditions. Thus, OE-MSCs represent a good source of Parkinson's stem cell-based therapy. In this research, we studied thirty male rats (n = 10 in each group) in three control (Ctl), lesion (LE), and intranasal administration (INA) groups to investigate the therapeutic effect of intranasal injection of OE-MSCs in the Parkinson's animal models. To do so, we examined the homing variation of OE-MSCs in different brain regions such as olfactory bulb (OB), cortex, striatum (Str), hippocampus (HPC), and substantia nigra (SN). The results of real-time PCR and immunohistochemistry (IHC) analysis showed the expression of dopaminergic neuron markers such as PITX3, PAX2, PAX5 (as dopaminergic neurons markers), tyrosine hydroxylase (TH), and dopamine transporter (DAT) 2 months after INA of 1 × 106 OE-MSCs. The results confirmed that IN OE-MSCs delivery into the central nervous system (CNS) was powerful enough to improve the behavioral functions in the animal models of PD.

Evaluation of Serum Levels of Transient Receptor Potential Cation Channel Subfamily V Member 1, Vasoactive Intestinal Polypeptide, and Pituitary Adenylate Cyclase-Activating Polypeptide in Chronic and Episodic Migraine: The Possible Role in Migraine Transformation.

Objectives: This study aimed to investigate the role of serum levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), vasoacive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP) in the development and also the transformation of migraine in patients suffering from migraine. Methods: Eighty-nine participants with a mean age of 39 years were divided into 23 episodic migraine (EM), 36 chronic migraine (CM), and 30 healthy control groups. Demographic, anthropometric, and headache characteristic information, and also blood samples, was collected. Serum levels of TRPV1, VIP, and PACAP were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Results: Based on our findings, the serum level of TRPV1 was significantly higher in CM compared to the control group (p < 0.05), whereas serum levels of VIP (p < 0.01) and PACAP (p < 0.05) in the EM group were significantly more than the control group. There was no significant difference between EM and CM groups. Conclusions: An elevation in the serum levels of TRVP1 among chronic migraineurs and increments in the levels of VIP and PACAP were observed among EM patients compared to healthy subjects. However, our data failed to demonstrate the probable role of these biomarkers in migraine progression, and more studies are needed to clarify the molecular mechanisms involved in migraine progression.

Glutamate Signaling Pathway in Absence Epilepsy: Possible Role of Ionotropic AMPA Glutamate Receptor Type 1 Subunit.

AMPA receptors, consisting of glutamate receptor type1 (GluR1) subunit are involved in the pathophysiology of some neurological disorders. In this study, the role of the GluR1 subunit in the development, as well as features of absence seizures were assessed. Both Wistar and WAG/Rij (a genetic animal model of absence epilepsy) rats with 2 and 6-month ages were included in the study. The expression of GluR1 was measured in the somatosensory cortex. Moreover, the effects of pharmacological activation and inhibition of AMPA receptors on the characteristic of absence epileptic activities were evaluated by microinjection of agonist or antagonist of AMPA receptors on the somatosensory cortex in the epileptic WAG/Rij rats. Distribution of the GluR1 subunit of AMPA receptors in the both IV (p < 0.001) and VI (p < 0.01) layers of the somatosensory cortex in the epileptic WAG/Rij rats was higher than non-epileptic animals. In addition, the microinjection of AMPA receptors agonist on the somatosensory cortex of the WAG/Rij rats increased both amplitude (p < 0.01) and duration (p < 0.001) of spike-wave discharges (SWDs), while injection of antagonist reduced amplitude (p < 0.001) and duration (p < 0.01) of SWDs in the somatosensory cortex of epileptic rats. The high expression of GluR1 in the somatosensory cortex of epileptic rats suggests the role of AMPA receptors consisting of the GluR1 subunit in the development of absence seizures. The modulatory effects AMPA receptors on the feature of SWDs suggest the potential of AMPA receptors antagonists as a therapeutic target for absence epilepsy.

Experimental Models of Absence Epilepsy.

INTRODUCTION: Absence epilepsy is a brief non-convulsive seizure associated with sudden abruptness in consciousness. Because of the unpredictable occurrence of absence seizures and the ethical issues of human investigation on the pathogenesis and drug assessment, researchers tend to study animal models. This paper aims to review the advantages and disadvantages of several animal models of nonconvulsive induced seizure. METHODS: The articles that were published since 1990 were assessed. The publications that used genetic animals were analyzed, too. Besides, we reviewed possible application methods of each model, clinical types of seizures induced, purposed mechanism of epileptogenesis, their validity, and relevance to the absence epileptic patients. RESULTS: The number of studies that used genetic models of absence epilepsy from years of 2000 was noticeably more than pharmacological models. Genetic animal models have a close correlation of electroencephalogram features and epileptic behaviors to the human condition. CONCLUSION: The validity of genetic models of absence epilepsy would motivate the researchers to focus on genetic modes in their studies. As there are some differences in the pathophysiology of absence epilepsy between animal models and humans, the development of new animal models is necessary to understand better the epileptogenic process and, or discover novel therapies for this disorder.

The organizational culture of Iran University of Medical Sciences from the viewpoint of faculty members.

Background: It has been widely acknowledged that change and constant modification is the key to survive for any organization among their rivals. Since success in implementing changes in the organization strongly depends on the organizational culture, this study aims to assess the organizational culture in Iran University of Medical Sciences. The results of this study can be beneficial in initiating a movement towards the third - and fourth generation of universities. Methods: This study is descriptive-correlational. The Organizational Culture Assessment Instrument (OCAI) was employed to collect data. A questionnaire was sent to the faculty members via email, and the responses were collected and analyzed. Results: Out of the 982 faculty members, 189 participated (20.7%) in this study. Analysis showed that the organizational culture of the university is congruent and harmonious and in the current state, it is primarily hierarchical (31%) and market-oriented (28%) with emphasis on stability and control in the organization. Whereas, faculty members tend to move the organizational culture of the university towards adhocracy (30%) and clan culture (29%). Conclusion: University administrators must strengthen the culture of innovation and creativity based on the needs of the market. This only can be achieved by supporting teamwork in their move towards desired change.

The effect of exercise on GABA signaling pathway in the model of chemically induced seizures.

AIMS: Gamma amino butyric acid (GABA) imbalance plays a critical role in most neurological disorders including epilepsy. This study assessed the involvement of mild exercise on GABA imbalance following by seizure induction in rats. MAIN METHODS: Seizure was induced by pentylentetrazole (PTZ) injection. Animals were divided into sham, seizure, exercise (EX), co-seizure-induced exercise (Co-SI EX) and Pre-SI EX groups. In the Co-SI EX group, doing exercise and seizure induction was carried out during four weeks. Animals in the Pre-SI EX group exercised in week 1 to week 8 and seizures were induced in week 5 to week 8. Seizure properties, neural viability and expressions of glutamic acid decarboxylase 65 (GAD65) and GABAA receptor α1 in the hippocampus were assessed. KEY FINDINGS: Seizure severity reduced and latency increased in the Co-SI EX and Pre-SI EX groups compared to seizure group. The mean number of dark neurons decreased in all exercise groups compared to seizure group in both CA1 and CA3 areas. The gene level of GAD65 and GABAA receptor α1 was highly expressed in the Co-SI EX group in the hippocampal area. Distribution of GAD65 in the both CA1 and CA3 areas increased in the EX and Co-SI EX groups. GABAA receptor α1 was up-regulated in the CA3 area of Co-SI EX group and down-regulated in the CA1 and CA3 areas of Pre-SI EX group. SIGNIFICANCE: These findings suggest that exercise develop anti-epileptic as well as neuroprotective effects by modulating of GABA disinhibition.

Discrepancies of Notch 1 receptor during development of chronic seizures.

The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer's disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end-stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end-stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures.

Stable Knockdown of Adenosine Kinase by Lentiviral Anti-ADK miR-shRNAs in Wharton's Jelly Stem Cells.

OBJECTIVES: In this study, we describe an efficient approach for stable knockdown of adenosine kinase (ADK) using lentiviral system, in an astrocytoma cell line and in human Wharton's jelly mesenchymal stem cells (hWJMSCs). These sources of stem cells besides having multilineage differentiation potential and immunomodulatory activities, are easily available in unlimited numbers, do not raise ethical concerns and are attractive for gene manipulation and cell-based gene therapy. MATERIALS AND METHODS: In this experimental study, we targeted adenosine kinase mRNA at 3' and performed coding sequences using eight miR-based expressing cassettes of anti-ADK short hairpin RNA (shRNAs). First, these cassettes with scrambled control sequences were cloned into expressing lentiviral pGIPZ vector. Quantitative real time-polymerase chain reaction (qRT-PCR) was used to screen multi-cassettes anti-ADK miR-shRNAs in stably transduced U-251 MG cell line and measuring ADK gene expression at mRNA level. Extracted WJMSCs were characterized using flow cytometry for expressing mesenchymal specific marker (CD44+) and lack of expression of hematopoietic lineage marker (CD45-). Then, the lentiviral vector that expressed the most efficient anti-ADK miR-shRNA, was employed to stably transduce WJMSCs. RESULTS: Transfection of anti-ADK miR-shRNAs in HEK293T cells using CaPO4 method showed high efficiency. We successfully transduced U-251 cell line by recombinant lentiviruses and screened eight cassettes of anti-ADK miRshRNAs in stably transduced U-251 MG cell line by qRT-PCR. RNAi-mediated down-regulation of ADK by lentiviral system indicated up to 95% down-regulation of ADK. Following lentiviral transduction of WJMSCs with anti-ADK miRshRNA expression cassette, we also implicated, down-regulation of ADK up to 95% by qRT-PCR and confirmed it by western blot analysis at the protein level. CONCLUSIONS: Our findings indicate efficient usage of shRNA cassette for ADK knockdown. Engineered WJMSCs with genome editing methods like CRISPR/cas9 or more safe viral systems such as adeno-associated vectors (AAV) might be an attractive source in cell-based gene therapy and may have therapeutic potential for epilepsy.

Developmental changes in Notch1 and NLE1 expression in a genetic model of absence epilepsy.

Childhood absence epilepsy (CAE) is an epilepsy syndrome with seizures occurring in the early childhood, highlighting that seizures susceptibility in CAE is dependent on brain development. The Notch 1 signalling pathway is important in brain development, yet the role of the Notch1 signalling pathway in CAE remains elusive. We here explored Notch1 and its modulator notchless homologue 1 (NLE1) expression in WAG/Rij and control rats using immunohistochemistry. Functional Notch 1 effects were assessed in WAG/Rij rats in vivo. WAG/Rij rats lack the developmental increase in cortical Notch1 and NLE 1 mRNA expression seen in controls, and Notch 1 and NLE1 mRNA and protein expression were lower in somatosensory cortices of WAG/Rij rats when compared to controls. This coincided with an overall decreased cortical GFAP expression in the early development in WAG/Rij rats. These effects were region-specific as they were not observed in thalamic tissues. Neuron-to-glia ratio as a marker of the impact of Notch signalling on differentiation was higher in layer 4 of somatosensory cortex of WAG/Rij rats. Acute application of Notch 1 agonist Jagged 1 suppressed, whereas DAPT, a Notch antagonist, facilitated spike and wave discharges (SWDs) in WAG/Rij rats. These findings point to Notch1 as an important signalling pathway in CAE which likely shapes architectural organization of the somatosensory cortex, a region critically involved in developmental epileptogenesis in CAE. More immediate effects of Notch 1 signalling are seen on in vivo SWDs in CAE, pointing to the Notch 1 pathway as a possible treatment target in CAE.

Effects of garlic extract on spreading depression: In vitro and in vivo investigations.

OBJECTIVES: The potential use of garlic for prevention and treatment of different types of headaches has been suggested by several medieval literatures. Cortical spreading depression (CSD), a propagating wave of neuroglial depolarization, was established as a target for anti-migraine drugs. This study was designed to investigate the effect of garlic extract on CSD in adult rats. METHODS: CSD was induced by KCl microinjection in the somatosensory cortex. The effects of five different concentrations of garlic oil (1-500 µl/l) were tested on different characteristic features of CSD in necocortical slices. In in vivo experiments, the effects of garlic oil on electrophysiological and morphological changes induced by CSD were investigated. RESULTS: Garlic oil in a dose-dependent manner decreased the amplitude of CSD but not its duration and velocity in neocortical brain slices. Garlic oil at concentration of 500 µl/l reversibly reduced the amplitude of the field excitatory post-synaptic potentials and inhibited induction of long-term potentiation in the third layer of neocortical slices. In in vivo studies, systemic application of garlic oil (1 ml/l) for three consecutive days reduced the amplitude and repetition rate of CSD. Garlic oil also prevented of CSD-induced reactive astrocytosis in the neocortex. DISCUSSION: Garlic oil suppresses CSD, likely via inhibition of synaptic plasticity, and prevents its harmful effects on astrocyte. Further studies are required to identify the exact active ingredient(s) of garlic oil that inhibit CSD and may have the potential to use in treatment of CSD-related disorders.

The Modulatory Effect of Metabotropic Glutamate Receptor Type-1α on Spike-Wave Discharges in WAG/Rij Rats.

Modulatory function of metabotropic glutamate type 1 (mGlu1) receptors plays a crucial role in the pathophysiology of some neurological disorders, including schizophrenia and epilepsy. In this study, the expression of mGlu1α receptors in the thalamic nuclei was assessed during development of absence seizures in the WAG/Rij rats, a valid genetic animal model of absence epilepsy. In addition, the effect of pharmacological modulation of mGlu1α receptors in the laterodorsal (LD) nucleus of the thalamus on the characteristic features of bioelectrical brain activities in the WAG/Rij rats was assessed. The expression of mGlu1α receptors in the LD was assessed in four experimental groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. Agonist and antagonist of mGlu1α receptors were infused in LD in the six months old WAG/Rij (epileptic) rats. The protein level of mGlu1α receptors in the thalamus of the 6-month-old WAG/Rij rats was lower than non-epileptic animals. In addition, the distribution of mGlu1α receptors in different thalamic nuclei was lower in the 6-month-old WAG/Rij compared to age-matched Wistar rats. The gene expression of mGlu1α receptor was also significantly lower in 6-month-old WAG/Rij rats in the LD compared to other animal groups. The microinjection of mGlu1α receptors agonist and antagonist in the LD reduced the duration of spike-wave discharges (SWDs) and increased the amplitude and duration of SWDs, respectively, in 6-month-old WAG/Rij rats. The alterations of mGlu1α receptors expression in the thalamus of epileptic WAG/Rij rats as well as its modulatory effects in the generation of SWDs suggest the potential of mGlu1 receptors as a therapeutic target in absence epilepsy.

Brain Derived Neurotrophic Factor Modification of Epileptiform Burst Discharges in a Temporal Lobe Epilepsy Model.

INTRODUCTION: Transforming Growth Factor-Beta 1 (TGF-ß1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-ß1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-ß1 and susceptibility to IS. METHODS: Male Wistar rats were divided into sham (receiving phosphate buffered saline within dorsal hippocampus), pilocarpine (epileptic model of TLE), single injection BDNF (epileptic rats which received single high dose of BDBF within dorsal hippocampus), and multiple injections BDNF (epileptic rats which received BDNF in days 10, 11, 12, and 13 after induction of TLE) groups. Their electrocorticogram was recorded and amplitude, frequency, and duration of spikes were evaluated. RESULTS: Amplitude and frequency of epileptiform burst discharges were significantly decreased in animals treated with BDNF compared to pilocarpine group. CONCLUSION: Our findings suggested that BDNF may modulate the epileptic activity in the animal model of TLE. In addition, it may have therapeutic effect for epilepsy. More studies are necessary to clarify the exact mechanisms of BDNF effects.

The neuroprotective effect of a triazine derivative in an Alzheimer's rat model.

UNLABELLED: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. It is characterized by formation of amyloid plaques and neurofibrillary tangles in the brain, degeneration of the cholinergic neurons and neural cell death. This study was aimed to investigate the effect of a triazine derivative, C16H12Cl2N3S, on learning in an Alzheimer's rat model. Animals were divided into seven groups; each group contained seven animals. CONTROL GROUP: animals received no surgery and treatment; saline group: animals received normal saline after recovery; sham group: animals received 10% DMSO after recovery; STZ group (Alzheimer's model): animals received streptozotocin (STZ) in four and six days after recovery; T5, T10 and T15 groups: animals were treated with triazine derivative, C16H12Cl2N3S, at doses of 5, 10 and 15 µM, respectively. All drugs were injected intracerebroventricular. The spatial learning and histological assessment were performed in all groups. Animals in STZ group had more deficits in spatial learning than the control group in Morris water maze. C16H12Cl2N3S improved spatial learning significantly compared to STZ group. The CA1 pyramidal layer thicknesses in STZ group were reduced significantly compared to control group. C16H12Cl2N3S increased the CA1 pyramidal layer thickness in T15 group compared to STZ group. Current findings suggest C16H12Cl2N3S may have a protective effect on learning deficit and hippocampal structure in AD.

Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI.