PURPOSE: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. METHODS: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered 80 µg/kg ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. RESULTS: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. CONCLUSION: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.
Animals ; Atrophy ; Carotid Artery, Common ; Corpus Callosum ; Dementia ; Dementia, Vascular ; Demyelinating Diseases ; Ghrelin ; Hippocampus ; Humans ; Learning ; Memory Disorders ; Memory ; Microvessels ; Models, Animal ; Molecular Biology ; Myelin Sheath ; Neuroprotection ; Pathology ; Rats ; Spatial Memory ; Vascular Endothelial Growth Factor A ; Water ; White Matter

White matter damage, characterized by demyelination due to the damage of oligodendrocyte precursor cells (OPCs), is the most common type of brain damage in preterm infants. Survivors are often subject to long-term neurodevelopmental sequelae because of the lack of effective treatment. In recent years, it has been found that cell transplantation has the potential for the treatment of white matter damage. OPCs are frequently used cells in cell transplantation therapy. With abilities of migration and myelinization, OPCs are the best seed cells for the treatment of white matter damage. Several studies have found that OPCs may not only replace impaired cells to reconstruct the structure and function of white matter, but also inhibit neuronal apoptosis, promote the proliferation of endogenous neural stem cells, and enhance the repairment of the blood-brain barrier. However, the clinical application of OPC transplantation therapy faces many challenges, such as the effectiveness, risk of tumorigenesis and immune rejection. With reference to these studies, this article reviewed the development of myelination, the obtainment of OPCs, the therapeutic mechanism as well as application research, and analyzed the current challenges of OPC transplantation, in order to provide a new direction for clinical treatment of white matter damage in preterm infants.
Cell Separation ; Demyelinating Diseases ; therapy ; Humans ; Infant, Newborn ; Infant, Premature ; Oligodendrocyte Precursor Cells ; transplantation ; White Matter ; pathology

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Animals ; Animals, Newborn ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Cell Differentiation ; drug effects ; physiology ; Cell Proliferation ; drug effects ; genetics ; Cells, Cultured ; Cuprizone ; toxicity ; Demyelinating Diseases ; chemically induced ; metabolism ; pathology ; Embryo, Mammalian ; Gene Expression Regulation, Developmental ; genetics ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Inbred C57BL ; Myelin Basic Protein ; metabolism ; Myelin Proteolipid Protein ; metabolism ; Myelin Sheath ; drug effects ; metabolism ; Oligodendroglia ; drug effects ; metabolism ; Protein-Tyrosine Kinases ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDNeuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice.

METHODSData including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables.

RESULTSTotally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups.

CONCLUSIONThe different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

Adolescent ; Adult ; Aquaporin 4 ; blood ; cerebrospinal fluid ; Autoantibodies ; blood ; cerebrospinal fluid ; Demyelinating Diseases ; blood ; cerebrospinal fluid ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis ; blood ; cerebrospinal fluid ; pathology ; Myelin-Oligodendrocyte Glycoprotein ; blood ; cerebrospinal fluid ; Neuromyelitis Optica ; blood ; cerebrospinal fluid ; pathology ; Retrospective Studies ; Young Adult

Balo's concentric sclerosis is regarded as a rare variant of multiple sclerosis. Traditionally, Balo's concentric sclerosis was a post-mortem diagnosis, but the recent introduction of brain magnetic resonance imaging (MRI) scans may allow noninvasive access without biopsy. Brain MRI findings of Balo's concentric sclerosis is characteristic concentric configuration of alternating bands of white matter of different pathology, with relatively preserved myelination alternating with regions of demyelination in the cerebral white matter. We report a case of Balo's concentric sclerosis with recurrent optic neuritis.
Biopsy ; Brain ; Demyelinating Diseases ; Diagnosis ; Diffuse Cerebral Sclerosis of Schilder* ; Humans ; Magnetic Resonance Imaging ; Multiple Sclerosis ; Myelin Sheath ; Optic Neuritis* ; Pathology

Alexander disease (ALXD) is a rare demyelinating disease of the white matter of the brain that is caused by a mutation in the glial fibrillary acidic protein (GFAP) gene. The overexpression of GFAP in astrocytes induces a failure in the developmental growth of the myelin sheath. The neurodegenerative destruction of the myelin sheath of the white matter is accompanied by an accumulation of abnormal deposits of Rosenthal fibers in astrocytes, which is the hallmark of ALXD. The disease can be divided into four groups based on the onset age of the patients: neonatal, infantile, juvenile, or adult. Early-onset disease is more severe, progresses rapidly, and results in a shorter life span than late-onset cases. Magnetic resonance imaging and genetic tests are mostly used for diagnostic purposes. Pathological tests of brain tissue for Rosenthal fibers are definitive diagnostic methods. Therapeutic strategies are being investigated. Ceftriaxone, which is an enhancer of glial glutamate transporter (GLT-1) expression, is currently in clinical trials for the treatment of patients with ALXD. To date, there are no clinically available treatments. The cause, pathology, pathophysiology, inheritance, clinical features, diagnosis, and treatment of ALXD will be reviewed comprehensively.
Adult ; Age of Onset ; Alexander Disease* ; Amino Acid Transport System X-AG ; Astrocytes ; Brain ; Ceftriaxone ; Demyelinating Diseases ; Diagnosis ; Glial Fibrillary Acidic Protein ; Humans ; Magnetic Resonance Imaging ; Methods ; Myelin Sheath ; Pathology ; Wills

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Astrocytoma ; metabolism ; pathology ; CD3 Complex ; metabolism ; Central Nervous System ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; Demyelinating Diseases ; diagnosis ; metabolism ; pathology ; Diagnosis, Differential ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Lymphoma ; metabolism ; pathology ; Magnetic Resonance Imaging

OBJECTIVETo explore HEPACAM mutations in a Chinese family with megalencephalic leukoencephaloptathy with subcortical cysts (MLC).

METHODGenomic DNA samples were extracted from peripheral blood of the proband and her parents. All exons and exon-intron boundaries of HEPACAM and MLC1 were amplified in the MLC family by polymerase chain reaction (PCR) followed by direct DNA sequencing.

RESULTTwo heterozygous mutations of HEPACAM located in exon 2, c.203A > T(p.K68M) and c.395C > A(p.T132N), were identified in the proband. The proband's mother had the heterozygous mutations c.203A > T(p.K68M), and her father had the heterozygous mutation-c.395C > A(p.T132N). There was no variation found in MLC1 gene.

CONCLUSIONThe proband was heterozygous compound MLC patient carrying on one allele with the c.203A > T(p.K68M) mutation inherited from her mother, and the other allele with the c.395C > A(p.T132N) mutation inherited from her father. The parents both are heterozygous carriers with normal phenotype. The disease-causing gene for this family was resulted in HEPACAM mutation other than MLC1 mutation.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Cysts ; genetics ; pathology ; DNA Mutational Analysis ; Exons ; Female ; Genotype ; Hereditary Central Nervous System Demyelinating Diseases ; genetics ; pathology ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics

OBJECTIVETo identify potential mutation in the MLC1 gene in a Chinese family affected with megalencephalic leukoencephalopathy and subcortical cysts (MLC), and to provide prenatal diagnosis.

METHODSGenomic DNA of the patients, their parents and younger sister were extracted from peripheral blood. That of the fetus was extracted from an amniotic fluid sample. A total of 12 exons and at least 100 bp flanking the intronic sequence of the MLC1 gene were amplified with PCR. MLC1 mutations were screened by sequencing. Linkage analysis was performed for the family to assure accuracy of prenatal diagnosis.

RESULTSThe two patients were both heterozygote for c.177_178delG (p.Ser60AlafsX5) mutation in exon 2 and c.598-2A>C change in intron 7. The c.177_178delG mutation was inherited from the father, and the c.598-2A>C mutation was inherited from the mother. The younger sister and the fetus have both inherited c.177_178delG from the father but did not inherit c.598-2A>C from the mother. Prenatal diagnosis suggested the fetus to be a carrier for a MLC1 mutation. Linkage analysis was consistent with the result of mutation detection. The fetus was born normal as predicted.

CONCLUSIONThe c.598-2A>C is a novel splicing mutation. Prenatal diagnosis through DNA sequencing and linkage analysis were performed for the first time on Chinese patients with MLC.

Adolescent ; Base Sequence ; Brain ; pathology ; Cysts ; diagnosis ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Genetic Linkage ; Genetic Testing ; Hereditary Central Nervous System Demyelinating Diseases ; diagnosis ; genetics ; Humans ; Magnetic Resonance Imaging ; Male ; Membrane Proteins ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis

Brain ; pathology ; Demyelinating Diseases ; complications ; diagnosis ; pathology ; Encephalomyelitis ; complications ; diagnosis ; pathology ; Fatal Outcome ; Humans ; Leukoencephalitis, Acute Hemorrhagic ; complications ; diagnosis ; pathology ; Magnetic Resonance Imaging ; Male ; Young Adult