The comparative effects of bone marrow mesenchymal stem cells and supernatant transplantation on demyelination and inflammation in cuprizone model.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with inflammation and immune dysfunction. OBJECTIVES: We compared the remyelination and immunomodulation properties of mesenchymal stem cells (MSCs) with their conditioned medium (CM) in the cuprizone model. METHODS: Twenty-four C57BL/ 6 mice were divided into four groups. After cuprizone demyelination, MSCs and their CM were injected into the right lateral ventricle of mice. The expression level of IL-1ß, TNF-α, and BDNF genes was evaluated using the qRT-PCR. APC antibody was used to assess the oligodendrocyte population using the immunofluorescent method. The remyelination and axonal repair were studied by specific staining of the LFB and electron microscopy techniques. RESULTS: Transplantation of MSCs and CM increased the expression of the BDNF gene and decreased the expression of IL-1ß and TNF-α genes compared to the cuprizone group, and these effects in the cell group were more than CM. Furthermore, cell transplantation resulted in a significant improvement in myelination and axonal repair, which was measured by luxol fast blue and transmission electron microscope images. The cell group had a higher number of oligodendrocytes than other groups. CONCLUSIONS: According to the findings, injecting MSCs intraventricularly versus cell-conditioned medium can be a more effective approach to improving chronic demyelination in degenerative diseases like MS.

Stem Cell-Derived Exosomal MicroRNAs as Novel Potential Approach for Multiple Sclerosis Treatment.

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation and demyelination of CNS neurons. Up to now, there are many therapeutic strategies for MS but they are only being able to reduce progression of diseases and have not got any effect on repair and remyelination. Stem cell therapy is an appropriate method for regeneration but has limitations and problems. So recently, researches were used of exosomes that facilitate intercellular communication and transfer cell-to-cell biological information. MicroRNAs (miRNAs) are a class of short non-coding RNAs that we can used to their dysregulation in order to diseases diagnosis. The miRNAs of microvesicles obtained stem cells may change the fate of transplanted cells based on received signals of injured regions. The miRNAs existing in MSCs may be displayed the cell type and their biological activities. Current studies show also that the miRNAs create communication between stem cells and tissue-injured cells. In the present review, firstly we discuss the role of miRNAs dysregulation in MS patients and miRNAs expression by stem cells. Finally, in this study was confirmed the relationship of microRNAs involved in MS and miRNAs expressed by stem cells and interaction between them in order to find appropriate treatment methods in future for limit to disability progression.

Maternal diabetes decreases the expression of α2-adrenergic and M2 muscarinic receptors in the visual cortex of male rat neonates.

AIMS: This study investigates the impact of maternal diabetes on the expression of α2-adrenergic and M2 muscarinic receptors in the primary visual cortex of male offspring born to diabetic rats. MAIN METHODS: In adult female rats, a single dose of intraperitoneal streptozotocin (STZ) was used to induce diabetes (Diabetic group). Diabetes was controlled with insulin in the Insulin-treated group. Female rats in the control group received normal saline instead of STZ. Male newborns were euthanized at P0, P7, and P14, and the expression of α2-adrenergic and M2 muscarinic receptors in the primary visual cortex was determined using immunohistochemistry (IHC). KEY FINDINGS: The study showed that α2-adrenergic and M2 muscarinic receptors were significantly suppressed in all layers of the primary visual cortex of male neonates born to diabetic rats at P0, P7, and P14 compared to the control group. The highest expression was for the Con group at P14 and the lowest one was in the Dia group at P0 for both receptors. The insulin treatment in diabetic mothers modulated the expression of these receptors to normal levels in their newborns. SIGNIFICANCE: The results demonstrate maternal diabetes decreases the expression of α2-adrenergic and M2 muscarinic receptors in the primary visual cortex of male offspring born to diabetic rats. Insulin treatment can offset these effects of diabetes.

Increased Apoptosis in Subcortical Regions of The Visual Pathway in Offspring Born to Diabetic Rats.

OBJECTIVE: Diabetes in pregnancy is a prevalent disease that can affect the central nervous system of the fetus by hyperglycemia. This study aimed to investigate the impact of maternal diabetes on neuronal apoptosis in the superior colliculus (SC) and the lateral geniculate nucleus (LGN) in male neonates born to diabetic mothers. MATERIALS AND METHODS: In this experimental study, female adult rats were separated into three groups: control, diabetic (induced using an intraperitoneal injection of streptozotocin), and insulin-treated diabetic [diabetes controlled by subcutaneous neutral protamine hagedorn (NPH)-insulin injection]. Male neonates from each group were euthanized on 0, 7, and 14 postnatal days (P0, P7, and P14, respectively), and apoptotic cells were identified using TUNEL staining. RESULTS: The numerical density per unit area (NA) of apoptotic cells was significantly higher in SC and the dorsal LGN (dLGN) in neonates born to the diabetic rats compared to the control group at P0, P7, and P14. However, insulin treatment normalized the number of apoptotic cells. CONCLUSION: This study demonstrated that maternal diabetes increased apoptosis in dLGN and SC of male neonates at P0, P7, and P14.

Expression of GABAAα1, GABAB1, and mGluR2 receptors in the lateral geniculate body of male neonates born to diabetic rats.

Objectives: Diabetes during gestation is one of the most common pregnancy complications and has adverse effects on offspring, including a negative impact on the offspring's central nervous system (CNS). Diabetes is a metabolic disease associated with visual impairment. Due to the importance of the lateral geniculate body (LGB) in the visual pathway, the present study examined the effect of maternal diabetes on the expression of gamma-aminobutyric acid (GABAAα1 and GABAB1) and metabotropic Glutamate (mGlu2) receptors in the LGB of male neonates of diabetic rats. Materials and Methods: Diabetes was induced in female adult rats by a single intraperitoneal dose of streptozotocin (STZ) 65 (mg/kg). In the Insulin-treated diabetic rats, diabetes was controlled by subcutaneous NPH-insulin injection daily. After mating and delivery, male offspring were killed by carbon dioxide gas inhalation at P0, P7, and P14 (postnatal days 0, 7, and 14). The expression of GABAAα1, GABAB1, and mGluR2 in the LGB of male neonates was determined using the immunohistochemistry (IHC) method. Results: The expression of GABAAα1 and GABAB1 was significantly reduced, whereas the expression of mGluR2 was markedly increased in the diabetic group compared with the control and insulin-treated groups at P0, P7, and P14. Conclusion: The results of the present study showed that induction of diabetes altered the expression of GABAAα1, GABAB1, and mGluR2 in the LGB of male neonates born to diabetic rats at P0, P7, and P14. Moreover, insulin treatment could reverse these effects of diabetes.

Maternal diabetes decreases the expression of GABAAα1, GABAB1, and mGlu2 receptors in the visual cortex of male rat neonates.

AIMS: This study examines the impact of maternal diabetes on the expression of GABAB1, GABAAα1, and mGlu2 receptors in the primary visual cortex layers of male rat newborns. MAIN METHODS: In diabetic group (Dia), diabetes was induced in adult female rats using an intraperitoneal dose of Streptozotocin (STZ) 65 (mg/kg). Diabetes was managed by daily subcutaneous injection of NPH insulin in insulin-treated diabetic group (Ins). Control group (Con) received normal saline intraperitoneally rather than STZ. Male offspring born to each group of female rats were euthanized via CO2 inhalation at P0, P7, and P14 days after delivery and the expression of GABAB1, GABAAα1, and mGlu2 receptors in their primary visual cortex was determined using immunohistochemistry (IHC). KEY FINDINGS: The expression of GABAB1, GABAAα1, and mGlu2 receptors increased gradually with age in the male offspring born to Con group while the highest expression was detected in layer IV of the primary visual cortex. In Dia group newborns, the expression of these receptors was significantly reduced in all layers of the primary visual cortex at every three days. Insulin treatment in diabetic mothers restored the expression of these receptors to normal levels in their newborns. SIGNIFICANCE: The study indicates that diabetes reduces the expression of GABAB1, GABAAα1, and mGlu2 receptors in the primary visual cortex of male offspring born to diabetic rats at P0, P7, and P14. However, insulin treatment can counteract these effects.

The Role of Microglial Depletion Approaches in Pathological Condition of CNS.

Microglia are the primary immune cells of the central nervous system (CNS) that comprise about 5-12% of all cells in the brain. These cells are the first line of defense that protects the CNS from damage and attacking pathogens. Microglia originate from yolk sac macrophages and migrate to the brain before the blood-brain barrier formation. Microglia show key roles in healthy CNS including promoting neurogenesis, synaptic sculpting, and maintaining homeostasis but in pathological conditions of CNS, microglial activation may exacerbate diseases. Thus, microglial depletion of the CNS is a novel approach that could be a useful tool to understand the microglial functions in neurodegenerative and neuroinflammatory diseases. There are methods for microglial ablation and reduction such as genetic tools and pharmacological inhibitors. In this study, we review recent studies that used different microglial ablation models for microglial reduction and repopulation after depletion in pathological states of CNS. Recently, studies showed that microglial depletion as a potential therapeutic application has benefits (such as inflammatory factors reduction, increase synaptogenesis, astrogliosis preventation) in CNS. For these reasons, the inhibition of microglia with these models was considered a therapeutic approach for neurodegenerative disease treatment.

Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper and lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, and cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology of ALS is still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, and neuroinflammation may be involved in the pathogenesis of ALS. From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) with Quinidine sulfate (Q), Edaravone, and Sodium phenylbutyrate with Taurursodiol (PB/TUDCO) have achieved FDA approval for ALS treatment. Despite the use of these four approved agents, the survival rate and quality of life of ALS patients are still low. Thus, finding novel treatments for ALS patients is an urgent requirement. Masitinib, a tyrosine kinase inhibitor, emphasizes the neuro-inflammatory activity of ALS by targeting macrophages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly reduces inflammation, and induces neuroprotection. Also, it was effective in phase 2/3 and 3 clinical trials (CTs) by increasing overall survival and delaying motor, bulbar, and respiratory function deterioration. This review describes the pathophysiology of ALS, focusing on Masitinib's mechanism of action and explaining why Masitinib could be a promising actor in the treatment of ALS patients. In addition, Masitinib CTs and other competitor drugs in phase 3 CTs have been discussed.

Combination Therapy of Mesenchymal Stem Cell Transplantation and Astrocyte Ablation Improve Remyelination in a Cuprizone-Induced Demyelination Mouse Model.

Astrocytes display an active, dual, and controversial role in multiple sclerosis (MS), a chronic inflammatory demyelination disorder. However, mesenchymal stem cells (MSCs) can affect myelination in demyelinating disorders. This study aimed to investigate the effect of single and combination therapies of astrocyte ablation and MSC transplantation on remyelination in the cuprizone (CPZ) model of MS. C57BL/6 mice were fed 0.2% CPZ diet for 12 weeks. Astrocytes were ablated twice by L-a-aminoadipate (L-AAA) at the beginning of weeks 13 and 14 whereas MSCs were injected in the corpus callosum at the beginning of week 13. Motor coordination and balance were assessed through rotarod test whereas myelin content was evaluated by Luxol-fast blue (LFB) staining and transmission electron microscopy (TEM). Glial cells were assessed by immunofluorescence staining while mRNA expression was evaluated by quantitative real-time PCR. Combination treatment of ablation of astrocytes and MSC transplantation (CPZ + MSC + L-AAA) significantly decreased motor coordination deficits better than single treatments (CPZ + MSCs or CPZ + L-AAA), in comparison to CPZ mice. In addition, L-AAA and MSCs treatment significantly enhanced remyelination compared to CPZ group. Moreover, combination therapy caused a significant decrease in the number of GFAP+ and Iba-1+ cells, whereas oligodendrocytes were significantly increased in comparison to CPZ mice. Finally, MSC administration resulted in a significant upregulation of BDNF and NGF mRNA expression levels. Our data indicate that transient ablation of astrocytes along with MSCs treatment improve remyelination through enhancing oligodendrocytes and attenuating gliosis in a chronic demyelinating mouse model of MS.

The distribution pattern of M2 and Adrenergicα2 receptors on inferior colliculi in male newborns of diabetic rats.

AIMS: Despite the high prevalence of diabetes in the world, its possible effects throughut pregnancy on neonatal auditory nervous system development are still unknown. In the present research, maternal diabetes' impact on the M2 and Adrenergicα2 receptors expression in the inferior colliculus (IC) of male newborn rats was investigated. MAIN METHODS: Female rats were grouped into three: sham, insulin-treated diabetic, and diabetic. Diabetes was induced through streptozotocin (STZ) injection as one dose intraperitoneally (65 mg/kg). After mating and delivery, male rats were euthanized on P0, P7, and P14. Immunohistochemistry (IHC) was used to study the distribution pattern of receptors. KEY FINDINGS: The present study indicated that the expression of M2 receptors in the diabetic group was significantly increased in pairwise comparisons in the sham and diabetic treated with insulin groups (P < 0.001, each). The highest M2 expression was for the diabetic group on P14 and the lowest one was for the sham group on P0. The Adrenergicα2a receptors expression in the diabetic group was significantly reduced in pairwise comparisons in the sham and diabetic treated with insulin groups (P < 0.001, each). The highest Adrenergicα2a expression was for the sham group on P14 and the lowest one was for the diabetic group on P0. There was no significant difference between the sham and insulin groups regarding all receptors expression. SIGNIFICANCE: This study demonstrated a time-dependent significant decrease in Adrenergicα2a but a time-dependent significant increase in M2 receptors expression.

Effects of mesenchymal stem cell transplantation on spinal cord injury patients.

Spinal cord injury (SCI) is a traumatic injury with sensory and motor deficits that more than 1 million patients worldwide suffer from disability due to it. Many pharmacological therapies help reduce SCI-related injury and protect CNS from more damage but no current therapy could improve the axonal repair. In this regard, stem cell therapy is considered a regenerative method for SCI patient treatment. The neurotrophic and immunomodulatory factor secretion, differentiation, neuroprotecting, and remyelinating properties have made mesenchymal stem cells (MSCs) principally useful in this field. There are studies on the role of MSCs in patients suffering from SCI. However, low number of SCI patients and the lack of control groups in these studies, the cell transplantation appropriate methods, including cell source, dose, route of delivery, and transplantation timing, are various in trials. This study reviews the beneficial effects of MSC transplantation in SCI clinical studies with a special focus on the MSC properties and limitations of MSC transplantation.

The effects of mesenchymal stem cells transplantation on A1 neurotoxic reactive astrocyte and demyelination in the cuprizone model.

Multiple sclerosis (MS), which is an autoimmune disease, is characterized by symptoms such as demyelination, axonal damage, and astrogliosis. As the most abundant type of glial cells, astrocytes play an important role in MS pathogenesis. Mesenchymal stem cells (MSCs) are a subset of stromal cells that have the potential for migration, immune-modulation, differentiation, remyelination, and neuroregeneration. Therefore, the present study evaluates the effects of MSC transplantation on A1 reactive astrocytes and the remyelination process in the cuprizone mouse model. The study used 30 male C57BL/6 mice, which were randomly distributed into three subgroups (n = 10), i.e., control, cuprizone, and transplanted MSCs groups. In order to generate a chronic demyelination model, the mice in the cuprizone group received food mixed with 0.2% cuprizone powder for 12 weeks. Then, 2 µl of DMEM containing approximately 3 × 105 DiI labeled cells was injected with a 4-min interval into the right lateral ventricle using a 10-µl Hamilton syringe. After 2 weeks of cell transplantation, we used the rotarod test to evaluate the behavioral deficits, while the remyelination process was assessed by transmission electron microscopy (TEM) and Luxol Fast Blue (LFB) staining. We assessed the population of A1 astrocytes and oligodendrocytes using specific markers, such as C3, GFAP, and Olig2, using the immunefleurocent method. The pro-inflammatory and trophic factors were assessed by a real-time polymerase chain reaction. According to our data, the specific marker of A1 astrocytes (C3) decreased in the MSCs group, while the number of oligodendrocytes significantly increased in this group compared to the cuprizone mice. Additionally, MSC was able to enhance the remyelination process after cuprizone usage, as shown by LFB and TEM images. The molecular results showed that MSCs could reduce pro-inflammatory factors, such as IL-1 and TNF-α, through the secretion of BDNF and TGF-ß as trophic factors. The obtained results indicated that MSC could reduce demyelination and inflammation by decreasing A1 neurotoxic reactive astrocytes and neurotrophic and immunomodulatory factors secretion in the chronic cuprizone demyelination model.

Effect of CSF1R inhibitor on glial cells population and remyelination in the cuprizone model.

Multiple sclerosis is a kind of autoimmune and demyelinating disease with pathological symptoms such as inflammation, myelin loss, astrocytosis, and microgliosis. The colony stimulating factor 1 receptor (CSF1R) is an essential factor for the microglial function, and PLX3397 (PLX) is its specific inhibitor. In this wstudy, we assessed the effect of different doses of PLX for microglial ablation on glial cell population and remyelination process. Sixty male C57BL/6 mice (8 weeks old) were divided into 6 groups. The animals were fed with 0.2% cuprizone diet for 12 weeks. For microglial ablation, PLX (290 mg/kg) was added to the animal food for 3, 7, 14 and 21 days. Glial cell population was measured using immunohistochemistry. The rate of remyelination was evaluated using electron microscopy and Luxol Fast Blue staining. The expression levels of all genes were assessed by qRT-PCR method. Data were analysed using GraphPad Prism and SPSS software. The results showed that the administration of different doses of PLX significantly reduced microglial cells (p ≤ .001). PLX administration also significantly increased oligodendrocytes population (p ≤ .001) and remyelination compared to the cuprizone mice, which was aligned with the results of LFB and TEM. Gene results showed that PLX treatment reduced CSF1R expression. According to the results, the administration of PLX for 21 days enhanced remyelination by increasing oligodendrocytes in the chronic demyelination model. These positive effects could be related to the reduction of microglia.

The effect of microglial ablation and mesenchymal stem cell transplantation on a cuprizone-induced demyelination model.

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with symptoms such as neuroinflammation, astrocytosis, microgliosis, and axonal degeneration. Mesenchymal stem cells (MSCs) with their immunomodulation, differentiation, and neuroprotection abilities can influence the remyelination process. The goal of this study is to investigate the impact of microglial ablation and MSCs transplantation on remyelination processes in the corpus callosum (CC) of the cuprizone demyelination model. For the induction of a chronic demyelination model, C57BL6 mice were fed with chow containing 0.2% cuprizone (wt/wt) for 12 weeks. For the depletion of microglia, PLX3397 was used as a colony-stimulating factor 1 receptor inhibitor for 21 days. MSCs were injected to the right lateral ventricle and after 2 weeks, the mice were killed. We assessed glial cells using specific markers such as APC, Iba-1, and GFAP using the immunohistochemistry method. Remyelination was evaluated by Luxol fast blue (LFB) staining and transmission electron microscope (TEM). The specific genes of microglia and MSCs were evaluated by a quantitative real-time polymerase chain reaction. According to the results of the study, 21 days of PLX3397 treatment significantly reduced microglial cells, and MSCs transplantation decreased the number of astrocytes, whereas the oligodendrocytes population increased significantly in PLX + MSC group in comparison with the cuprizone mice. Furthermore, PLX and MSC treatment elevated levels of remyelination compared with the cuprizone group, as confirmed by LFB staining and TEM analysis. The molecular results showed that MSC transplantation significantly decreased the number of microglia through the CX3CL1/CX3CR1 axis. These results revealed that PLX3397 treatment and MSCs injection reduced microgliosis and astrocytosis. It also increased the oligodendrocytes population by enhancing remyelination in the CC of the cuprizone model of MS.

Effects of mesenchymal stem cells transplantation on multiple sclerosis patients.

Multiple Sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) with symptoms such as neuroinflammation and axonal degeneration. Existing drugs help reduce inflammatory conditions and protect CNS from demyelination and axonal damage; however, these drugs are unable to enhance axonal repair and remyelination. In this regard, cell therapy is considered as a promising regenerative approach to MS treatment. High immunomodulatory capacity, neuro-differentiation and neuroprotection properties have made Mesenchymal Stem Cells (MSCs) particularly useful for regenerative medicine. There are scant studies on the role of MSCs in patients suffering from MS. The low number of MS patients and the lack of control groups in these studies may explain the lack of beneficial effects of MSC transplantation in cell therapies. In this review, we evaluated the beneficial effects of MSC transplantation in clinical studies in terms of immunomodulatory, remyelinating and neuroprotecting properties of MSCs.

Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone-induced demyelination model.

Microglial cells have an essential role in neurodegenerative disorders, such as multiple sclerosis. They are divided into two subgroups: M1 and M2 phenotypes. Mesenchymal stem cells (MSC), with neuroprotective and immunomodulating properties, could improve these diseases. We evaluate the immunomodulating effects of MSC on microglial phenotypes and the improvement of demyelination in a cuprizone (CPZ) model of multiple sclerosis (MS). For inducing the chronic demyelination model, C57BL6 mice were given a diet with 0.2% CPZ (w/w) for 12 weeks. In the MSC group, cells were transplanted into the right lateral ventricle of mice. The expression of targeted genes was assessed by real-time polymerase chain reaction. M1 and M2 microglial phenotypes were assessed by immunohistochemistry of inducible nitric oxide synthase (iNOS) and Arg-1, respectively. Remyelination was studied by luxal fast blue (LFB) staining and electron microscopy (EM). We found that MSC transplantation reduced the expression level of M1-specific messenger RNA (mRNA; iNOS and CD86) but increased the expression level of M2 specific genes (CD206, Arg-1, and CX3CR1) in comparison to the CPZ group. Moreover, cell therapy significantly decreased the M1 marker (iNOS+ cells), but M2 marker (Arg-1+ cells) significantly increased in comparison with the CPZ group. In addition, MSC treatment significantly increased the CX3CL1 expression level in comparison with the CPZ group and led to improvement in remyelination, which was confirmed by LFB and EM images. The results showed that MSC transplantation increases the M2 and decreases the M1 phenotype in MS. This change was accompanied by decrease in demyelination and axonal injury and indicated that MSCs have a positive effect on MS by modification of microglia cells.

Effect of mesenchymal stem cells on glial cells population in cuprizone induced demyelination model.

Mesenchymal stem cells (MSCs) have a notable potential to modulate immune responses and protect the central nervous system (CNS), mostly by secreting factors that affect inflammation. MSCs have the ability to improve several autoimmune diseases in animal models including multiple sclerosis (MS). MS is a disease of the CNS among adult humans and it is characterized by demyelination, neuroinflammation and gliosis. In this study, we first induced chronic demyelination by cuprizone, followed by intraventricular injection of MSC. Our results showed that MSC significantly decreased microgliosis and astrocytosis by secreting cytokines that have neuroprotective activity including TGF-ß and CX3CL1. Also, downregulation of IL-1ß and TNF-α as inflammatory chemokines was seen along with decreased astrocytes and microglia activation. Finally, these results showed that trophic factors secreted by MSC can increase oligodendrocyte population and remyelination rate by reducing pro-inflammatory factors. These findings demonstrate that MSC could decrease inflammation, gliosis and demyelination with neuroprotective and immunomodulating properties in chronic cuprizone demyelination model. Therefore MSC transplantation can be considered as a suitable approach for enhancing myelination and reducing inflammation in diseases such as MS.

Astrocyte ablation induced by La-aminoadipate (L-AAA) potentiates remyelination in a cuprizone demyelinating mouse model.

Chronic demyelination in the central nervous system (CNS) is accompanied by an increase in the number of reactive astrocytes and astrogliosis. There are controversial issues regarding astrocytes and their roles in demyelinating diseases in particular for multiple sclerosis (MS). We aimed to evaluate possible roles for pharmacologic astrocyte ablation strategy using La-aminoadipate (L-AAA) on remyelination in a cuprizone model of demyelination. Male C57BL/6 mice were fed with 0.2% cuprizone for 12 weeks followed by 2-week administration of L-AAA through a cannula inserted 1 mm above the corpus callosum. Rotarod test showed a significant decrease in the range of motor coordination deficits after ablation of astrocytes in mice receiving cuprizone. Results of Luxol fast blue (LFB) and transmission electron microscopy (TEM) for evaluation of myelin content within the corpus callosum revealed a noticeable rise in the percentage of myelinated areas and in the number of myelinated fibers after L-AAA administration in the animals. Astrocyte ablation reduced protein expressions for GFAP (an astrocyte marker) and Iba-1 (a microglial marker), but increased expression of Olig2 (an oligodendrocyte marker) assessed by immunofluorescence. Finally, expression of genes related to recruitment of microglia (astrocyte chemokines CXCL10 and CXCL12) and suppression of oligodendrocyte progenitor cell (OPC) differentiation (astrocyte peptides ET-1 and EDNRB) showed a considerable decrease after administration of L-AAA (for all p < 0.05). These results are indicative of improved remyelination after ablation of astrocytes possibly through hampering microgliosis and astrogliosis and a further rise in the number of matured Olig2+ cells.