The use of cellulose has considerable promise in a wide range of industrial applications but is hampered by degradation in mechanical properties due to ambient moisture uptake. Existing models of equilibrium moisture content can predict the impact of these effects, but at present, the dynamical, atomic-scale picture of water ingress into cellulose is lacking. The present work reports nonequilibrium molecular simulations of the interface between cellulose and water aimed at capturing the initial stages of two simultaneous dynamical processes, water ingress into cellulose and cellulose dissolution into water. These simulations demonstrate that the process depends on the temperature and chain length in the amorphous region, where high temperatures can induce more mass exchange and short chains can easily detach from amorphous cellulose. A cooperative mechanism that involves both chemical and physical aspects, namely, hydrogen bonding and chain intertwining, respectively, is proposed to interpret the incipient dual ingress/dissolution process. Outcomes of this work will provide a foundation for cellulose functionalization strategies to impede moisture uptake and preserve the mechanical properties of nanocellulose in applications.
Running exercise, one of the strategies to protect brain function, has positive effects on neurons and synapses in the cortex and hippocampus. However, white matter, as an important structure of the brain, is often overlooked, and the effects of long-term running exercise on white matter are unknown. Here, 14-month-old male Sprague-Dawley (SD) rats were divided into a middle-aged control group (18-month-old control group), an old control group (28-month-old control group), and a long-term runner group (28-month-old runner group). The rats in the runner group underwent a 14-month running exercise regime. Spatial learning ability was tested using the Morris water maze, and white matter volume, myelinated fiber parameters, total mature oligodendrocyte number, and white matter capillary parameters were investigated using stereological methods. The levels of growth factors related to nerve growth and vascular growth in peripheral blood and the level of neurite outgrowth inhibitor-A (Nogo-A) in white matter were measured using an enzyme-linked immunosorbent assay (ELISA). The present results indicated that long-term running exercise effectively delayed the age-related decline in spatial learning ability and the atrophy of white matter by protecting against age-related changes in myelinated fibers and oligodendrocytes in the white matter. Moreover, long-term running exercise prevented age-related changes in capillaries within white matter, which might be related to the protective effects of long-term exercise on aged white matter.
Introduction To quantitatively investigate the capillaries within the white matter of Tg2576 Alzheimer's disease (AD) transgenic mice during the early stage. Methods In the current study, 10-month-old male Tg2576 AD mice were used as the early-stage AD group and age-matched nontransgenic littermate mice were used as the wild-type group. Then, the Morris water maze was used to examine the spatial learning and memory abilities of the mice in both groups, and unbiased stereological methods were used to accurately quantify the volume of white matter and the parameters of the capillaries within the white matter, such as the total length, total volume, and total surface area of capillaries. Results The Morris water maze performance of the Tg2576 group was worse than that of the wild-type group, while the white matter volume did not significantly differ between the wild-type group and the Tg2576 group. The total length, total volume, and total surface area of the capillaries within the white matter of the Tg2576 group were significantly decreased compared to those of the wild-type group. Conclusions The current study provide structural basis for understanding the pathological changes of the early stage of AD and cognitive decline in AD might be associated with changes in the white matter capillaries. Capillaries within the white matter might, thus, serve as a valid target for the prevention and treatment of early-stage AD.
SummaryBackgroundThis paper was carried out based on two motivations: (a) prior studies achieved mixed results regarding the effect of passive smoking on depression; and (b) studies on the impacts of passive smoking usually neglect effects on older people. In our paper, we studied the causal effect of passive smoking at home on depression among older people aged 60 years and older in China with a longitudinal study.MethodsIn assessing the causal relationship, we developed a fixed‐effects instrumental variable method using an exogenous variable—health consciousness and the smoking status of parents—as instruments of smoking status. We used data from the China Health and Retirement Longitudinal Study (CHARLS), which provides a national, high‐quality, and longitudinal household survey of people aged 45 years and older.ResultsOur empirical results reveal that passive smoking at home increased the depressive symptoms of older people, regardless of their smoking status. Moreover, the impact of passive smoking on depression is larger for nonsmokers than smokers. Additionally, the health consciousness and smoking status of parents are effective instrumental variables.ConclusionsThis paper calls for governments and medical institutions to pay more attention to the health of older people and their need for healthy living environments.
Objective: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT. Methods: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulinlike growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT. Results: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without shortterm therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05). Conclusion: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.
Hematopoietic stem cell transplantation is only suitable for early-stage adrenoleukodystrophy (ALD). In this study, we observed the therapeutic efficacy of combined transplantation of neural precursor cells (NPCs) and olfactory ensheathing cells (OECs) on late-stage X-linked ALD in nine children who were admitted in our hospital between June 2009 and January 2014. Related patient information included onset time 3 months to 1 year, magnetic resonance imaging (MRI) score 11.02 +/- 0.90, and neurologic function score 2-3. All patients received combined transplantation of NPCs and OECs by injection around the lateral angle of the frontotemporal-occipital lesion under MRI guidance. It was found that the visual function, sleep, and communication obstacles were improved significantly without evidence of disease progression in six (66.7%) of the nine patients within 1 month after transplantation. In two of the six patients, the lesions became significantly smaller than before, although their MRI scores remained unchanged significantly. In addition, cell therapy did not induce any irreversible adverse event during the study period, indicating that combined transplantation of NPCs and OECs was safe and reliable, and could improve the clinical manifestations of ALD in children within a short time. Although this cell therapy was not able to halt the progression of the disease 1-3 months after transplantation, it could still be used as an early treatment and provide patients with more opportunities for hematopoietic stem cell transplantation, which is the only effective long-term treatment for X-linked ALD at present. The preliminary results from this study suggest that a comprehensive prevention strategy of serial and combined transplantation may improve some functions for ALD patients in the short-term, however, long-term effects need further study.
Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is characterized by deficits in cognition and memory. Although amyloid-β (Aβ) accumulation is known to be the earliest pathological event that triggers subsequent neurodegeneration, how Aβ accumulation causes behavioral deficits remains incompletely understood. In this study, using the Morris water maze test, ELISA and stereological methods, we examined spatial learning and memory performance, the soluble Aβ concentration and the myelination of fibers in the hippocampus of 4-, 6-, 8- and 10-month-old Tg2576 AD model mice. Our results showed that spatial learning and memory performance was significantly impaired in the Tg2576 mice compared to the wild type (WT) controls and that the myelinated fiber length in the hippocampal dentate gyrus (DG) was markedly decreased from 0.33 ± 0.03 km in the WT controls to 0.17 ± 0.02 km in the Tg2576 mice at 10 months of age. However, the concentrations of soluble Aβ40 and Aβ42 were significantly increased as early as 4-6 months of age. The decreased myelinated fiber length in the DG may contribute to the spatial learning and memory deficits of Tg2576 mice. Therefore, we suggest that the significant accumulation of soluble Aβ may serve as a preclinical biomarker for AD diagnosis and that protecting myelinated fibers may represent a novel strategy for delaying the progression of early-stage AD.
Cognition and memory decline with normal aging, which could be partly attributed to the degeneration of brain white matter. Previous studies demonstrated that exposure to an enriched environment (EE) could protect cognition and memory from aging. However, if or how EE might affect the brain white matter has not been thoroughly investigated. In the current study, 24 middle-aged (14-month-old) female Sprague -Dawley (SD) rats were randomly assigned to EE or standard environment (SE) for 4 months. At the end of the environment intervention, the Morris water maze tests were performed. Then, 5 rats were randomly selected from each group for stereological assessment of the brain white matter and its myelinated fibers. The results revealed that middle-aged rats living in EE displayed better spatial learning than SE controls. The white matter volume was 124.6 ± 7.8mm(3) in EE rats, which was significantly enlarged compared with 84.8 ± 3.4mm(3) in SE rats. Likewise, the myelinated fiber volume was markedly increased from 56.6 ± 1.7 mm(3) in SE rats to 87.2 ± 9.0mm(3) in EE rats; so was the myelinated fiber length from 83.5 ± 6.6 km in SE rats to 119.0 ± 10.0 km in EE rats. Our data suggested that EE could protect brain white matter and its myelinated fibers of female rats at middle age.
目的 定量研究Tg2576转基因AD小鼠大脑白质内毛细血管的改变.方法 随机选取10月龄雄性Tg2576小鼠和同窝生相同月龄雄性野生型小鼠(Wild-type)各11只.应用Morris水迷宫检测其空间学习和记忆能力.行为学测试后在每组小鼠内各随机选取7只,应用冰冻切片技术、免疫组织化学技术及体视学方法定量研究大脑白质体积以及白质内毛细血管的总长度、总体积和总表面积.结果 10月龄Tg2576转基因AD小鼠的定位航行测试显示其逃避潜伏期显著长于同月龄野生型小鼠(P<0.05),而空间探索试验结果无显著差异.10月龄Tg2576转基因AD小鼠大脑白质内毛细血管的总长度、总体积和总表面积(6.90±0.82 m,0.0648±0.0167mm3,61.77±13.80 mm2)均较同月龄野生型小鼠(12.44士2.64m,0.0891±0.0145 mm3,106.81±20.17mm2)显著降低(P<0.01,P<005,P<0.01),而两组小鼠的大脑白质体积无显著性差异.结论 出现行为学改变的10月龄Tg2576转基因AD小鼠大脑白质内存在显著性毛细血管改变,这可能是造成白质损伤和早期学习记忆能力减退的重要原因,而白质内毛细血管可能作为早期预防和治疗AD的靶点.
White matter degenerates with normal aging and accordingly results in declines in multiple brain functions. Previous neuroimaging studies have implied that the white matter is plastic by experiences and contributory to the experience-dependent recovery of brain functions. However, it is not clear how and how far enriched environment (EE) plays a role in the white matter remodeling. Male rats exhibit earlier and severer age-related damages in the white matter and its myelinated fibers than female rats; therefore, in this current study, 24 middle-aged (14-month-old) and 24 old-aged (24-month-old) male SD rats were randomly assigned to an EE or standard environment (SE) for 4 months prior to Morris water maze tests. Five rats from each group were then randomly sampled for stereological assessment of the white matter. Results revealed that EE could somewhat induce improvement of spatial learning and significantly increase the white matter volume, the myelinated fiber volume and the myelinated fiber length during normal aging. The EE-induced improvement of spatial learning ability was significantly correlated with the EE-induced increase of the white matter and its myelinated fibers. We suggested that exposure to an EE could delay the progress of age-related changes in the white matter and the effect could extend to old age.
目的:研究双环己酮草酰二腙(cuprizone,CPZ)诱导C57BL/6小鼠建立的精神分裂症样模型小鼠海马内有髓神经纤维体积改变及其与行为学改变之间的关系.方法:19只雄性6周龄小鼠,随机分为实验组(9只)和对照组(10只),实验组用含0.2%(质量分数百分比,w/w)CPZ的混合鼠饲料饲喂6周,建立精神分裂症样小鼠模型;对照组用标准鼠饲料饲喂6周.运用旷场实验、高架十字迷宫实验、Morris水迷宫实验、转棒实验和探孔实验测试行为学改变;髓鞘碱性蛋白(myelin basic protein,MBP)免疫组化染色及透射电镜定性观察髓鞘结构变化;体视学方法测量并计算海马总体积及海马内有髓神经纤维体积;统计学方法分析行为学改变与海马内有髓神经纤维体积改变之间的关系.结果:与对照组相比,实验组小鼠体质量下降,差异具有统计学意义(P<0.05);行为学实验结果表明:实验组小鼠存在异常的焦虑行为(P=0.018)及空间认知能力障碍(P=0.037),但运动能力(P=0.443)、探索习性(P=-0.306)及学习记忆能力未见受损(P=0.462);MBP免疫组化染色发现海马区域免疫阳性染色变浅;透射电镜定性观察发现海马内有髓神经纤维存在脱髓鞘改变;体视学定量测定发现,实验组小鼠海马总体积未发生显著性改变(P=0.955),而海马内有髓神经纤维体积减小(P=0.009);统计学相关分析发现,闭臂路程百分比和海马内有髓神经纤维体积呈正相关(rs=0.83,P=0.003),开臂路程百分比和海马内有髓神经纤维体积呈负相关(rs=-0.65,P=0.043).结论:进一步证实CPZ模型小鼠可以出现类似精神分裂症样症状的行为学改变及海马内有髓神经纤维存在脱髓鞘改变,并且发现海马内有髓神经纤维体积和行为学表现间具有一定的相关性.
ABSTRACT The decline of hippocampus‐dependent learning and memory during normal aging is not associated with neuron death and synapse loss. Until now, age‐related changes in the myelinated fibers of the hippocampus have not been investigated. Therefore, in this study, the myelinated fibers in the hippocampi of young (6 months), middle‐aged (18 months), and old‐aged (28 months) male Sprague‐Dawley rats were studied with transmission electron microscope and stereological methods, following spatial learning tests in a Morris water maze. The results showed that hippocampus‐dependent spatial learning was impaired in old‐aged rats but that the total volume, length, and mean diameter of the myelinated fibers in the hippocampus, as well as the hippocampal volume, remained constant during the normal aging process. Our results suggest that the age‐related decline in hippocampus‐dependent spatial learning is not attributable to myelinated fiber changes in the hippocampus and that other, undetermined factors are responsible. Anat Rec, 297:1490–1497, 2014. © 2014 Wiley Periodicals, Inc.
Objective To explore an appropriate dose of cuprizone(CPZ) for the CPZ-fed animal model as a novel schizophrenia animal model,and to investigate the possible relationship among CPZ dose,demyelination of nerve fibers in hippocampus and behavior alternations in CPZ-fed mice.Methods C57BL /6 mice were fed with 0.2%,0.3% and 0.4%(w / w) of CPZ for 6 weeks,respectively,and the mice without any treatment were used as control.The body weight,survival time and behavior changes were compared between the CPZ-fed mice and the control mice.The myelin basic protein(MBP)-positive nerve fibers in CA1 and DG regions of hippocampus were stained with immunohistochemical methods,and the mean optical density(OD) of MBP-positive nerve fibers in the hippocampal CA1 and DG regions of each group were calculated and compared.The changes of the myelinated nerve fibers in CA1 and DG regions of hippocampus between the control group and 0.2% CPZ group were investigated with a stereological method.Results The survive time of the 0.4% CPZ group was significantly less than that of control group(P < 0.01).The body weight of the CPZ-fed groups was significantly lower than that of the control group(P < 0.05),and the weight loss increased along with the increase of CPZ doses.In open field test,the mice fed with 0.2% of CPZ spent significantly more time in the central area of box compared with the control group(P < 0.05).The ODs of MBP-positive fibers in CA1 region of hippocampus in the 0.2% CPZ group and 0.3% CPZ group were significantly lower than that in the control group(P < 0.01).The OD of MBP-positive fibers in DG region of hippocampus in the 0.2% CPZ group was significantly lower than that in the control group and 0.3% CPZ group(P < 0.01).The volumes of CA1 and DG regions of the hippocampus in the 0.2% CPZ group were not significantly different from those in the control group(P > 0.05).The length density and total length of the myelinated nerve fibers in CA1 and DG regions of hippocampus in the 0.2% CPZ group were significantly less than those in the control group(P < 0.05).Conclusion 0.2% CPZ(w / w) was the appropriate dose for CPZ-fed animal model to mimic schizophrenia.The myelinated fibers in CA1 and DG regions of hippocampus undergo demyelination when mice are exposed to 0.2% CPZ for 6 weeks.
Recently, increasing evidences have indicated that abnormal behavior and white matter changes had appeared before senile plaques were formed in Alzheimer's disease (AD). However, the exact nature of these changes in behavior and white matter structure in early AD are unclear. This study used the Morris water maze, an ELISA assay, a transmission electron microscopic technique and new stereological methods to investigate the behavior, Aβ protein expression and white matter structure of Tg2576 transgenic mice at four ages. Only 10 months of age, the time latency in the Morris water maze tasks for Tg2576 transgenic mice were significantly longer than that of wild-type mice. The concentration of Aβ40 protein in the white matter of the Tg2576 transgenic mice was significantly increased in four ages mice, but the Aβ42 protein was significantly increased only in the 6-month-old mice. In 10-month-old mice, the axon volume in the white matter of the Tg2576 transgenic mice was significantly decreased when compared to the wild-type mice. These results suggest that the deposition of Aβ in the white matter of Tg2576 transgenic mice appeared before the spatial memory decline. The early detection of the Aβ content in the white matter of AD might help diagnose suspected AD. In addition, the axon changes in the white matter of AD might be one of the morphological causes of the behavioral deficits observed in 10-month-old transgenic mouse models of AD, and protecting the axons in the white matter might be an important method for delaying the progression of AD.
Objective To investigate the changes of cerebral cortex volume and myelinated fibers in the cerebral cortices of cuprizone(CPZ)-induced schizophrenia-like mice.Methods Six-week old male C57BL/6 mice were divided into a CPZ group and a control group.The mice in the CPZ group were fed with mixed standard rodent chow containing 0.2% CPZ,while those in the control group were fed with standard lab chow.After six weeks,behavioral tests were performed to confirm the success of schizophrenia-like animal model.Then the cerebral cortex volume and myelinated fibers in the cerebral cortices were determined with transmission electron microscopy and stereological methods.Results Mice in the CPZ group showed schizophrenia-like performance.Stereological results showed that there was no significant change in the volume of the cerebral cortex between CPZ group and control group(P>0.05).Compared with the control group,the length density and total length of myelinated fibers in the cerebral cortices of the CPZ group significantly decreased by 64.3% and 68.9%,respectively(P<0.01).Compared with the control group,the mean diameter of myelinated fibers in the CPZ group significantly increased by 17.8%(P<0.01),and the total length of the myelinated fibers with diameters of 0.2 to less than 0.4 μm,0.4 to less than 0.6 μm and 0.6 to less than 0.8 μm significantly decreased by 4.317,3.313 and 0.940 km,respectively(P<0.01).There was no significant difference in the total length of other myelinated fibers between the two groups.Conclusion In CPZ group,the total length of myelinated fibers in cerebral cortex decreases but the mean diameter of the myelinated fibers increases,which is due to the loss of small-diameter myelinated fibers.
It had been reported that enriched environment was beneficial for the brain cognition and for the neurons and synapses in hippocampus. Previous study reported that the oligodendrocyte density in hippocampus was increased when the rats were reared in the enriched environment from weaning to adulthood. However, biological conclusions based on density were difficult to interpret because the changes in density could be due to an alteration of total quantity and/or an alteration in the reference volume. In the present study, we used unbiased stereological methods to investigate the effect of enriched environment on the total number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) positive cells in CA1 and dentate gyrus (DG) of the hippocampus in aged rats. Our results indicated that there was significant difference in the total numbers of CNPase positive cells in both CA1 and DG between enriched environment group and standard environment group. The present study provided the first evidence for the protective effects of enriched environment on the CNPase positive cells in aged hippocampus.
Objective To investigate the changes of the myelinated fibers in the corpus callosum of the cuprizone(CPZ)-induced mouse model of schizophrenia,and the relationship between the demyelination changes and the behavioral abnormalities in this animal model.Methods Nineteen male C57BL/6 mice were randomly divided into 2 groups,control group(n=10) and CPZ-treated group(n=9).The mice in the later group were fed with a diet of 0.2%(w/w) CPZ mixed into standard rodent chow for 6 weeks.The mice in control group were fed standard lab chow and lab water.The behavioral changes of the animals were investigated with a series of behavioral tests.The changes of the corpus callosum and the myelinated fibers in the corpus callosum were studied with immunohistochemical assay,transmission electron microscopy and stereological methods.Results The CPZ-treated mice displayed more activities in the central area of open field(P<0.05)and in the open arms of elevated plus maze(P<0.05),which suggested that the anxiety behavior in the CPZ-treated mice was reduced when compared to the control.Morris water maze demonstrated that there was no working memory deficit in the CPZ-treated mice compared to the control(P>0.05).There was no abnormality in the motor function and basic exploration ability in the CPZ-treated mice when compared to the control.There were demyelination changes in the corpus callosum of the CPZ-treated mice.There was no significant difference in the total volume of the corpus callosum between the CPZ-treated mice and the control(12.66±1.07 vs 13.53±2.79 mm3).The length density and total length of the myelinated fibers in the corpus callosum were significantly decreased in CPZ-treated mice than control mice(0.70±0.17 vs 1.47±0.17 km/mm3,9.06±2.56 vs 19.75±3.70 km,P<0.05).Conclusion CPZ-treated mice display schizophrenia-like behaviors and demyelination change in the corpus callosum.
Objective To explore the role of white matter injuries in the schizophrenia induced by the NMDA re-ceptor antagonist. Methods Adult male C57BL/6J mice (8 week old) were equally divided into four groups. One group was sub-chronically treated with saline solution, and the other three groups were intraperitoneally treated with MK-801 at dose of 0.025 mg/mL (M1), 0.050 mg/mL (M2) and 0.100 mg/mL (M3) in a volume 10 ml per kilogram body weight. All ani-mals were tested using Morris water maze at the 9th-15th day and using the Hole Board exploration as well as Rota Rod performance tests on the 16th day. The myelin basic protein (MBP) and the ultrastructure of the myelin sheaths in the cor-pus callosum were then examined using immunohistochemical methods, transmission electron microscope technique and stereological methods. Results The repeated sub-chronic MK-801 treatment did not induce impairment of spatial learning and memory in Morris water maze. The MK-801 treatment at 0.25 mg/kg and 1.00 mg/kg but not at 0.50 mg/kg resulted in less exploration to a new environment. The myelin staining with anti-MBP antibody was less intense in all three schizo-phrenic groups when compared to saline control group (P<0.01). Furthermore, MK-801 treatment caused pathological al-terations of the myelin sheaths including segmental demyelination of myelinated fibers and splitting of myelin sheath lamel- lae in schizophrenic groups. The ratio of the injured myelinated nerve fibers in the corpus callosum of MK-801 treated mice [M3 group, (22.42 ± 4.24)%] was significantly higher when compared to the control mice [(3.84 ± 1.35)%,P<0.01)]. Conclusions The present study demonstrated the white matter damages, mainly low MBP expression and segmental demye-lization in the corpus callosum in the mice sub-chronic treated with MK-801, indicating that the white matter changes might be involved in the schizophrenia induced by NMDA antagonist.
In this study, the effect of enriched environment (EE) on the spatial learning of aged rats was examined, and then the effects of EE on the aged corpus callosum (CC) were investigated by means of the modern stereological methods. We found that EE significantly improved the spatial learning of aged rats. The CC volume, the total volume of the myelinated fibers and total volume of the myelin sheaths in the CC, the total length of the myelinated fibers in the CC of enriched rats were significantly increased when compared to standard rats. The increase of the myelinated fibers in enriched rat CC might provide one of the structural bases for the enrichment‐related improvement of the spatial learning. This study provided, to the best of our knowledge, the first evidence of environmental enrichment‐induced increases of the CC and the myelinated fibers in the CC of aged rats. Anat Rec, , 2012. © 2012 Wiley Periodicals Inc.
Normal aging is commonly associated with decreased cognitive functions, which could be conspicuously alleviated by enriched environment (EE) with physical, social, and sensory stimuli, suggesting that aging brain still has intriguing plasticity. Multiple researches have been carried out to explore the structural and the molecular changes in aging brain, which would be considered for evidences that EE regulated brain plasticity. Because there is no significant neuron loss in aging cerebral cortex and the white matter is crucial for cognitive functions, this review focused on the age‐related white matter changes and the effects of EE on aged white matter. Data from our stereology laboratory revealed that age‐related spatial memory declines had more to do with white matter alterations, which were due to marked demyelination and loss of oligodendrocytes in the white matter. We also demonstrated that EE recovered spatial memory impairment and increased white matter volume by promoting marked remyelination in aged brain. This review approached the issue that EE might contribute to normal aging and be beneficial for those suffering from demyelinated diseases. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.