BackgroundMultiple Sclerosis (MS) is a demyelinating disease leading to long-term neurological deficit due to unsuccessful remyelination and axonal loss. Currently, there are no satisfactory treatments for progressive MS somewhat due to the lack of an adequate animal model for studying the mechanisms of disease progression and screening new drugs.New methodLysolecithin (LPC) or agarose-gel loaded LPC (AL-LPC) were applied to mouse optic nerve behind the globe via a minor surgery. Agarose loading was used to achieve longer time of LPC exposure and subsequently long-lasting demyelination.ResultsThe lesion sites characterized by luxol fast blue (LFB), FluoroMyelin, Bielschowsky’s staining, and immunostaining showed extensive demyelination an

Objective: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The autoimmune pathology and long-term inflammation lead to substantial demyelination. These events lead to a substantial loss of oligodendrocytes (OLs), which in a longer period, results in axonal loss and long-term disabilities. Neural cells protection approaches decelerate or inhibit the disease progress to avoid further disability. Previous studies showed that metformin has beneficial effects against neurodegenerative conditions. In this study, we examined possible protective effects of metformin on toxin-induced myelin destruction in adult mice brains.Materials and Methods: In this experimental study, lysophosphatidylcholine (LPC) was used to i

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. TLE is characterized by recur‑rent, spontaneous seizures that originate from the temporal lobe (Falconer et al., 1964). The main thera‑peutic intervention for epileptic patients is antiepilep‑tic drugs, but 20–30% of epileptic patients are drug re‑sistant (Schmidt and Schachter, 2014). Therefore, more research has been dedicated to finding new therapies for epilepsy.Over the last decade, deep brain stimulation has been suggested as a treatment for patients with drug‑resistant epilepsy and patients who are not sur‑gical resection candidates (Jobst et al., 2010). Low fre‑quency stimulation (LFS), in the range of 0.5 to 5 Hz, has been shown to suppress seiz

AimInsulin resistance and neuroinflammation play roles in Alzheimer's (AD) etiology. Insulin receptors (IR) are developmentally expressed in neurons as well as astrocytes. Moreover, prolonged stress can induce brain insulin resistance and astrogliosis. Also, prenatal stress could advance AD-related abnormalities in a transgenic model of AD. Besides, postnatal maternal care (PMC) has antagonistic effects on prenatal stress (PS)-induced neuronal and immunological malfunctions. Using an icv-STZ subclinical model of sAD, we assessed PS and/or abnormal PMC impacts on advancing sAD-like pathology in adult male rats. We also sought astrocyte- and/or neuron-oriented change in central insulin programming.Main methodsPregnant rats were exposed to PS.

Removal of chondroitin sulfate proteoglycans (CSPGs) with chondroitinase ABC I (ChABC) facilitates axonal plasticity, axonal regeneration and remyelination, following injury to the central nervous system (CNS). However, the ChABC rapidly undergoes thermal inactivity and needs to be injected repeatedly. Here this limitation was overcame by immobilizing the ChABC on porous silicon (PSi) nanoparticles (ChABC@PSi). The efficacy of immobilized ChABC on CSPGs level and the demyelination insult was assessed in mice corpora callosa demyelinated by 6?weeks cuprizone (CPZ) feeding. ChABC@PSi was able to reduce the amount of CSPGs two weeks after animals treatment. CSPGs digestion by ChABC@PSi reduced the extent of demyelinated area as well as the ast

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 expression of NMDA subunit mRNA in hippocampal slices. The slope of field excitatory postsynaptic potential (fEPSP) was unaffected while the population spike amplitude and area were increased by a transient period of PTZ treatment (3?mM, 10?min). After a theta burst, a brief PTZ exposure can lead to an enhancement of LTP as documented by fEPSP recording. The effect can be blocked by a s

Introduction: Spinal cord injury (SCI) is a condition which can lead to permanent loss of neurons, glial and precursor cells. According to the positive influences of electrical stimulation in the neurogenesis, we hypothesized that sub-threshold electrical stimulation in the presence of exogenous astrocyte may trigger the differential regulation of wingless-type3 (Wnt-3) and eukaryotic initiation factor-2α (eIF2α) mediators in spinal cord injured rats. Results: The results show that expression of Wnt-3 and eIF2α proteins significantly enhanced after 14 days in the electrical stimulation+ SCI+ astrocyte group in comparison with SCI and SCI+ astrocyte groups. Also, the expression of GFAP cells was significantly increased after 14 days by el

Noradrenergic neurons of the locus coeruleus (LC) receive projection from hypothalamus orexinergic neurons and express orexin 1 receptor (Orx1). Orx in the locus coeruleus nucleus is involved in the development of morphine dependence. The downstream signaling of Orx contribution to the development of morphine dependence in LC neurons of morphine-dependent rats was studied. Therefore, we evaluated cyclic adenosine monophosphate (cAMP), cAMP response element-binding protein (CREB) and phospholipase Cβ3 (PLCβ3) levels by the application of immunohistochemistry. Results showed that cAMP, CREB and PLCβ3 levels were suppressed by the application of SB-334867 (as a selective Orx1 antagonist) in morphine-dependent rats. Our results unraveled tha

AimsWe still do not have effective treatment for hippocampal demyelination and memory deficit, the two common comorbidities in multiple sclerosis (MS). This study aimed to assess the therapeutic effect of Piperine (the main alkaloid of black pepper) in an experimental model of demyelination.Main methodsDemyelination was induced in male Wistar rats by bilateral injection of lysolecithin (LPC) into the CA1 region of the hippocampus. Piperine (5, 10, 20 mg/kg) was daily injected intraperitoneally three days post LPC injection for ten days. The spatial memory was examined by the Morris water maze task. Demyelination and astrocyte activation were assessed by an immunohistological study. The gene expression analysis of TNF-α, IL1-β, NF-κB, I

Background Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease that mainly affects optic nerves and spinal cord. Besides, loss of motor and cognitive function has been reported as important symptoms of disease. Objective Here we investigated the mitochondrial dysfunction and metabolic alterations in NMO patients and evaluate their correlation with disease progress, disability and cognitive impairment. Methods The individuals (12 controls and 12 NMO) were assessed for disease severity by expanded disease status scale (EDSS), cognitive function via symbol digit modalities test (SDMT) and fine motor disability by 9-hole peg test (9-HPT). We have measured Sirtuin 1 (SIRT1), SIRT3, mitochondrial complex I, complex IV, aconita