Javad Mirnajafi-Zadeh

Tarbiat Modares University | TMU · Department of Physiology

Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapeutic procedures. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel...

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT 3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT 3 receptor on the severity of seizures and learning and memory impairment by ele...

We aimed to study how morphine affects synaptic transmission in the dentate gyrus and CA1 regions along the hippocampal long axis. For this, recording and measuring of field excitatory postsynaptic potentials (fEPSPs) were utilized to test the effects of repeated morphine exposure on paired‐pulse evoked responses and long‐term potentiation (LTP) at...

Aims: Deep brain electrical stimulation (DBS), as a potential therapy for drug resistive epileptic patients, has inhibitory action on epileptogenesis. In the present investigation, the role of dopamine D2 -like receptors in the antiepileptogenic action of DBS was studied. Methods: Seizures were induced in adult rats by stimulating the perforant...

Dopamine may be involved in the anticonvulsant action of deep brain stimulation (DBS). Therefore, ventral tegmental area (VTA), as a brain dopaminergic nucleus, may be a suitable target for DBS anticonvulsant action. This study investigated the effect of tonic and phasic stimulations of the VTA on seizure parameters. Seizures were induced in adult...

Low frequency deep brain electrical stimulation (LFS) is a potential therapeutic strategy to control seizures in epilepsy patients. Given the functional connection of the olfactory bulb with the hippocampal formation, in this study the effect of applying LFS in the olfactory bulb on seizure severity, and learning and memory was investigated in hipp...

Temporal lobe epilepsy is the most drug-resistant type with the highest incidence among the other focal epilepsies. Metabolic manipulations are of great interest among others, glycolysis inhibitors like 2-deoxy d-glucose (2-DG) being the most promising intervention. Here, we sought to investigate the effects of 2-DG treatment on cellular and circui...

Temporal lobe epilepsy is the most drug-resistant type with the highest incidence among the other focal epilepsies. Metabolic manipulations are of great interest among others, glycolysis inhibitors like 2-deoxy d-glucose (2-DG) being the most promising intervention. Here, we sought to investigate the effects of 2-DG treatment on cellular and circui...

Understanding the pathogenesis of epilepsy including changes in synaptic pathways can improve our knowledge about epilepsy and development of new treatments. In this regard, data-driven models such as artificial neural networks, which are able to capture the effects of synaptic plasticity, can play an important role. This paper proposes long short...

Neural synchrony in brain circuits is the mainstay of cognition, including memory processes. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that disrupts neural synchrony in specific circuits, associated with memory dysfunction before a substantial neural loss. Recognition memory impairment is a prominent cognitive symptom in...

Low-frequency deep brain stimulation (LFS) inhibits neuronal hyperexcitability during epilepsy. Accordingly, the use of LFS as a treatment method for patients with drug-resistant epilepsy has been proposed. However, the LFS antiepileptic mechanisms are not fully understood. Here, the role of metabotropic glutamate receptors group I (mGluR I) in LFS...

There are many differences among dorsal and ventral hippocampal neural circuits that affect the synaptic plasticity. In this study we compared the occurrence of short-term plasticity in the field excitatory post synaptic potentials (fEPSP) in dorsal and ventral hippocampal CA1 area following kindled seizures. Animals (male C57 B6/J mice, 12 weeks o...

Background: Cannabinoid system affects memory and has anticonvulsant effects in epileptic models. In the current study, the role of cannabinoid 1 (CB1) receptors was investigated in amelioration of the effects of low-frequency stimulation (LFS) on learning and memory impairments in kindled rats. Methods: Electrical stimulation of the hippocampal...

The present study aimed to select an effective Pulsed High Magnetic Field (PHMF) stimulation protocol that would induce the Blood-Brain Barrier’s (BBB) reversible permeability to enhance brain-targeted drug delivery. PHMF was applied to the skull over the right hemisphere of 60 Wistar rats. The sham group contained other 10 rats that did not receiv...

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS’ inhibitory mechanisms is lacking. Here, α1 and α2 adrenergic receptors’ roles in mediating LFS inhibitory action on high-K⁺ induced epileptiform activity (EA) was examined in rat hippocampal slices. Materials and meth...

In spite of long-term intensive scientific research efforts, there are still many issues concerning the mechanisms of epileptogenesis and epilepsy to be resolved. Temporal lobe, in particular hippocampus, is vulnerable to epileptogenic process. Herein, electrical kindling model of temporal lobe were analyzed using proteomic approach. A dramatic dec...

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spe...

The Inhibitory effect of electrical low-frequency stimulation (LFS) on neuronal excitability and seizure occurrence has been indicated in experimental models, but the precise mechanism has not established. This investigation was intended to figure out the role of α1 and α2 adrenergic receptors in LFS' inhibitory effect on neuronal excitability. Epi...

Kindling results in abnormal synaptic potentiation and significant impairment in learning and memory. Electromagnetic field (EMF) effects on learning and memory in kindled animals and its effects on hippocampal neural activity are largely unknown. In the current study, the effects of EMF on learning and memory, as well as hippocampal synaptic plast...

Understanding the pathogenesis of epilepsy including changes in synaptic pathways can improve our knowledge about epilepsy and development of new treatments. In this regard, data-driven models such as artificial neural networks, which are able to capture the effects of synaptic plasticity, can play an important role. This paper proposes long short...

Allergic rhinitis (AR) is a chronic inflammatory disease frequently associated with a deficit in learning and memory. Working memory is an important system for decision making and guidance, which depends on interactions between the ventral hippocampus (vHipp) and the prelimbic prefrontal cortex (plPFC). It is still unclear whether AR influences the...

Mechanical ventilation (MV) can result in long-term brain impairments that are resistant to treatment. The mechanisms underlying MV-induced brain function impairment remain unclear. Since nasal airflow modulates brain activity, here we evaluated whether reinstating airflow during MV could influence the memory performance of rats after recovery. Rat...

Epileptic seizures are accompanied by learning and memory impairments. In this study, the effect of low frequency stimulation (LFS) on spatial learning and memory was assessed in kindled animals and followed for one month. Fully kindled rats received LFS at 4 times (immediately, 6 h, 24 h and 30 h following the final kindling stimulation). Applying...

Abstract This paper reports on the design, development, and test of a multi-channel wireless micro-electrocorticography (µECoG) system. The system consists of a semi-implantable, ultra-compact recording unit and an external unit, interfaced through a 2.4 GHz radio frequency data telemetry link with 2 Mbps (partially used) data transfer rate. Encase...

This paper reports on the design, development, and test of a multi-channel wireless micro-electrocorticography (µECoG) system. The system consists of a semi-implantable, ultra-compact recording unit and an external unit, interfaced through a 2.4 GHz radio frequency data telemetry link with 2 Mbps (partially used) data transfer rate. Encased in a 3D...

Alzheimer disease (AD) is a complex neurodegenerative disorder with no definite treatment. The expression of miR-29 family is significantly reduced in AD, suggesting a part for the family members in pathogenesis of the disease. The recent emergence of microRNA (miRNA)-based therapeutic approaches is emphasized on the efficiency of miRNA transfer to...

Introduction: In this study, the role of A1 adenosine receptors in improving the effect of Low-Frequency Electrical Stimulation (LFS) on seizure-induced hyperexcitability of hippocampal CA1 pyramidal neurons was investigated. Methods: A semi-rapid hippocampal kindling model was used to induce seizures in male Wistar rats. Examination of the electro...

Herein field recordings were utilized to test the effects of a transient period of pentylenetetrazol (PTZ) treatment on theta-burst long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses as well as RT-PCR was used to investigate the effects of the combination of the pharmacological treatment and the theta-burst LTP induction on the ex...

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, Gi-protein-coupled receptors, including D2-like receptors, may have a role in mediating these effects. In the present study, the role of D2-like receptors in LFS’ anti-seizure action was investigated. Rats were kindle...

Objectives: Cell therapy has provided clinical applications to the treatment of motor neuron diseases. The current obstacle in stem cell therapy is to direct differentiation of stem cells into neurons in the neurodegenerative disorders. Biomaterial scaffolds can improve cell differentiation and are widely used in translational medicine and tissue...

Epilepsy is the most common neurological disease with no definitive method in treatment. Notably, the main way to treat and control epileptic seizures is drug therapy. However, about 20-30% of patients with epilepsy are drug resistant and require other therapeutic manners. Deep brain stimulation is a new therapeutic strategy for these patients. Con...

Despite years of research on pain comorbidity with affective disorders and cognitive deficits, it is still unclear how deficit in attention co-occurs with chronic pain. It is likely that altered neuroplasticity and or dysregulated neurotransmitters induced by chronic pain, at which pain and cognitive processing systems overlap, may have a negative...

Anxiety is prevalent in asthma, and is associated with disease severity and poor quality of life. However, no study to date provides direct experimental evidence for the effect of allergic inflammation on the structure and function of medial prefrontal cortex (mPFC) and amygdala, which are essential regions for modulating anxiety and its behavioral...

Objective(s): Seizure detection during online recording of electrophysiological parameters is very important in epileptic patients. In the present study, online analysis of field potential recordings was used for detecting spontaneous seizures in epileptic animals. Materials and Methods: Epilepsy was induced in rats by pilocarpine injection. During...

Background The precise effect of low frequency stimulation (LFS) as a newly postulated, anticonvulsant therapeutic approach on seizure-induced changes in synaptic transmission has not been completely determined. Hypothesis In this study, the LFS effect on impaired, synaptic plasticity in kindled rats was investigated. Methods Hippocampal kindled...

The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orex...

Adipose derived stem cells (ADSCs) are multipotent and can transdifferentiate into neural stem cells. We investigated the transdifferentiation of ADSCs to neural phenotype (NP) cells using selegiline and two-dimensional electrophoresis (2-DE). The perinephric and inguinal fat of rats was collected and used to isolate ADSCs that were characterized b...

Allergic rhinitis is a chronic inflammatory disease of the upper respiratory tract, which is associated with high incidence of anxiety symptom. There is evidence that medial prefrontal cortex modulates anxiety-related behaviors and receives projections from olfactory bulb. Since olfactory dysfunction has been reported in allergic rhinitis, we aimed...

Glioblastoma multiforme (GBM) is a grade 4 and the most aggressive form of glioma, with a poor response to current treatments. The expression of microRNAs (miRNAs) is widely dysregulated in various cancers, including GBM. One of the overexpressed miRNAs in GBM is miR-21 which promotes proliferation, invasion and metastatic behaviors of tumor cells....

Low frequency stimulation (LFS) has anticonvulsant effect and may restore the ability of long-term potentiation (LTP) to the epileptic brain. The mechanisms of LFS have not been completely determined. Here, we showed that LTP induction was impaired following in vitro epileptiform activity (EA) in hippocampal slices, but application of LFS prevented...

Low-frequency stimulation has demonstrated promising seizure suppression in animal models of epilepsy, while the mechanism of the effect is still debated. Changes in intrinsic properties have been recognized as a prominent pathophysiologically relevant feature of numerous neurological disorders including epilepsy. Here, it was evaluated whether LFS...

Acute opioid withdrawal syndrome is a series of neurological symptoms caused by the abrupt cessation of the chronic administration of opioids such as morphine. The locus coeruleus (LC) in the brain stem receives a dense projection of orexinergic fibers from the hypothalamus and is a candidate site for the expression of the somatic aspects of morphi...

Low frequency stimulation (LFS) has inhibitory effect on hyperexcitability during epileptic states. However, knowledge is lacking about LFS patterns that can exert an optimal antiepileptic effect. In this study, the effect of different numbers of pulses and current intensities of 1 Hz LFS applied at various time points of epileptiform activity was...

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) in which multiple sites of blood-brain barrier (BBB) disruption, focal inflammation, demyelination and tissue destruction are the hallmarks. Here we show that sphingosine-1-phosphate receptor 2 (S1PR2) has a negative role in myelin repair as well as an important role...

Objective Electrical low frequency stimulation (LFS) is a new therapeutic method that moderates hyperexcitability during epileptic states. Seizure occurrence is accompanied by some changes in action potential (AP) features. In this study, we investigated the inhibitory action of LFS on epileptiform activity (EA) induced-changes in AP features in hi...

Locus coeruleus nucleus (LC) is a major noradrenergic nucleus in the brain. It receives dense orexinergic projections from lateral hypothalamus. Whilst it is known that orexin A increases firing rate of LC neurons, its effect on spontaneous and evoked inhibitory postsynaptic currents (sIPSCs and eIPSCs, respectively) has not been yet identified. In...

Introduction: Administration of low-frequency electrical stimulation (LFS) at the kindling site has an antiepileptogenic effect. In the present study, we investigated the role of cannabinoid receptors type 1 (CB1) in mediating the inhibitory effects of LFS on the development of perforant path kindled seizures. Methods: For seizure generation, ra...

Introduction: The signaling pathways involved in the antiepileptogenic effect of low frequency electrical stimulation (LFS) have not been fully understood. In the present study the role of extracellular signal-regulated kinase (ERK) signaling cascade was investigated in mediating the inhibitory effects of LFS on kindled seizures. Methods: Animal...

Low frequency electrical stimulation (LFS) is a potential therapeutic method for epilepsy treatment. However, the effect of different LFS characteristics including the number of pulses, intensity and the time of application on its antiepileptic action has not been completely determined. In the present study, epileptiform activity (EA) was induced i...

Background We aimed to investigate the potential prophylactic and curative effects of rosmarinic acid, one of the main constituents of rosemary, on the neuropathic pain induced by chronic constriction injury (CCI) in rats. Materials and methods CCI was used to induce peripheral neuropathic pain. In prophylactic groups, rosmarinic acid (10, 20, and...

Introduction: The life quality of patients with epileptic seizures is highly affected by cognitive deficits. Low Frequency Stimulation (LFS) is a novel approach for the treatment of pharmacoresistant epilepsy. The main goal of this research is investigating the possible effect of LFS on seizure-induced cognitive dysfunction. Methods: To this end...

Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain...

Objective: For human embryonic stem cells (hESCs) to differentiate into neurons, enormous changes has to occur leading to trigger action potential and neurotransmitter release. We attempt to determine the changes in expression of voltage gated channels (VGCs) and their electrophysiological properties during neural differentiation. Materials and m...

G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investiga...

Opioids have always been used in clinical practice for pain management. However, development of tolerance to their effects following long term administration, seriously restricts further clinical use of these drugs. In this regard, μ-opioid receptor (MOR) desensitization, as an initial step in development of opioid tolerance, is of particular signi...

Early enriched environment (EE) prevents several deficits associated with postnatal MK-801 [N-Methyl-D-Aspartate (NMDA) receptor antagonist] treatment such as cognitive and locomotor deficits. We sought physiological correlates to such changes by looking at inhibitory synaptic inputs onto pyramidal cells in a prefrontal cortex slice preparation. Ph...

Objective Low-frequency stimulation (LFS) exerts suppressive effects in kindled animals. It is believed that overstimulated glutamatergic and decreased GABAergic transmission have long been associated with seizure activity. In this study, we investigated the effect of electrical LFS on different parameters of spontaneous excitatory and inhibitory p...