Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after Traumatic Central Nervous System Injury.

Endogenous neural progenitor cell niches have been identified in adult mammalian brain and spinal cord. Few studies have examined human spinal cord tissue for a neural progenitor cell response in disease or after injury. Here, we have compared cervical spinal cord sections from 14 individuals who died as a result of nontraumatic causes (controls) with 27 who died from injury with evidence of trauma to the central nervous system. Nestin immunoreactivity was used as a marker of neural progenitor cell response. There were significant increases in the percentage of ependymal cells that were nestin positive between controls and trauma cases. When sections from lumbar and thoracic spinal cord were available, nestin positivity was seen at all three spinal levels, suggesting that nestin reactivity is not simply a localized reaction to injury. There was a positive correlation between the percentage of ependymal cells that were nestin positive and post-injury survival time but not for age, postmortem delay, or glial fibrillary acidic protein (GFAP) immunoreactivity. No double-labelled nestin and GFAP cells were identified in the ependymal, subependymal, or parenchymal regions of the spinal cord. We need to further characterize this subset of ependymal cells to determine their role after injury, whether they are a population of neural progenitor cells with the potential for proliferation, migration, and differentiation for spinal cord repair, or whether they have other roles more in line with hypothalamic tanycytes, which they closely resemble.

Uncovering novel roles of nonneuronal cells in body weight homeostasis and obesity.

Glial cells, which constitute more than 50% of the mass of the central nervous system and greatly outnumber neurons, are at the vanguard of neuroendocrine research in metabolic control and obesity. Historically relegated to roles of structural support and protection, diverse functions have been gradually attributed to this heterogeneous class of cells with their protagonism in crescendo in all areas of neuroscience during the past decade. However, this dramatic increase in attention bestowed upon glial cells has also emphasized our vast lack of knowledge concerning many aspects of their physiological functions, let alone their participation in numerous pathologies. This minireview focuses on the recent advances in our understanding of how glial cells participate in the physiological regulation of appetite and systemic metabolism as well as their role in the pathophysiological response to poor nutrition and secondary complications associated with obesity. Moreover, we highlight some of the existing lagoons of knowledge in this increasingly important area of investigation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuroblastic apoptosis in the subventricular zone is caused by 1-methy-4-phenylpiridinium (MPP(+)) converted from MPTP through MAO-B.

Intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration induces apoptosis of subventricular zone (SVZ) doublecortin (Dcx)-positive neural progenitor cells (migrating neuroblasts, A cells). Actually, a metabolite of MPTP, 1-methy-4-phenylpiridinium (MPP(+)), is responsible for neural progenitor cell toxicity. In the present study, to examine whether the MPTP-induced SVZ cell apoptosis is caused directly by MPP(+) metabolized through monoamine oxidase B (MAO-B), MPTP or MPP(+) was intracerebroventricularly (icv) injected into C57BL/6 mice. At Day 1 postinjection, many terminal deoxynucleotidyl transferase-mediated dUTP endlabeling (TUNEL)-positive cells were observed in the SVZ of both low (36 µg) and high (162 µg) dose MPTP- and MPP(+)-injected mice. The number of Dcx-positive A cells showed a significant decrease following high dose of MPTP- or MPP(+)-injection on Days 1 and 3, respectively, whereas that of EGFR-positive C cells showed no change in mice with any treatment. In addition, prior icv injection of a MAO-B inhibitor, R(-)-deprenyl (deprenyl), inhibited MPTP-induced apoptosis, but not MPP(+)-induced apoptosis. MAO-B- and GFAP-double positive cells were detected in the ependyma and SVZ in all mice. It is revealed from these results that icv injection of MPTP induces apoptosis of neural progenitor cells (A cells) in the SVZ via MPP(+) toxicity. In addition, it is suggested that the conversion from MPTP to MPP(+) is caused mainly by MAO-B located in ependymal cells and GFAP-positive cells in the SVZ.

Mesencephalic ependymal cysts: treatment under pure endoscopic or endoscope-assisted keyhole conditions.

OBJECT: Primary intracranial ependymal cysts are extremely rare. Similar to congenital intraparenchymal cysts in the mesencephalon they usually occur with symptoms of an occlusive hydrocephalus or symptoms like Parinaud syndrome, dizziness, or gait disturbance. The objective of this study was to evaluate the surgical methods for the treatment of these cysts and the clinical outcome of the patients. METHODS: The authors present the clinical records of 8 patients who were treated in their department for symptomatic mesencephalic ependymal cysts in the past 10 years. The patient age ranged from 22 to 60 years with a mean age of 44 years. In 4 cases the authors performed a suboccipital infratentorial supracerebellar approach by using endoscope-assisted microsurgery. The other 4 patients underwent a pure endoscopic procedure over a frontal bur hole trepanation. RESULTS: Four patients became symptom free, and the remaining 4 improved significantly after a mean follow-up duration of 38.5 months (range 5-119 months). One patient underwent 2 operations: first a ventriculocystostomy and 4 months later endoscopic third ventriculostomy because of recurrent hydrocephalus. In 1 case a second surgery was necessary because of a wound infection. In all of the patients an adequate fenestration of the cyst was achieved. CONCLUSIONS: A symptomatic mesencephalic ependymal cyst is an indication for neurosurgical intervention. These cysts can be treated successfully and most likely definitively by a pure endoscopic or endoscope-assisted keyhole neurosurgical technique. There were no morbid conditions or death due to the procedures in this group of 8 patients. Therefore, the authors regard these surgical procedures to be good alternatives to treatments such as shunt placement or stereotactic aspiration of the cysts.

Peroxisomal multifunctional protein-2 deficiency causes motor deficits and glial lesions in the adult central nervous system.

In humans, mutations inactivating multifunctional protein-2 (MFP-2), and thus peroxisomal beta-oxidation, cause neuronal heterotopia and demyelination, which is clinically reflected by hypotonia, seizures, and death within the first year of life. In contrast, our recently generated MFP-2-deficient mice did not show neurodevelopmental abnormalities but exhibited aberrations in bile acid metabolism and one of three of them died early postnatally. In the postweaning period, all survivors developed progressive motor deficits, including abnormal cramping reflexes of the limbs and loss of mobility, with death at 6 months. Motor impairment was not accompanied by lesions of peripheral nerves or muscles. However, in the central nervous system MFP-2-deficient mice overexpressed catalase in glial cells, accumulated lipids in ependymal cells and in the molecular layer of the cerebellum, exhibited severe astrogliosis and reactive microglia predominantly within the gray matter of the brain and the spinal cord, whereas synaptic and myelin markers were not affected. This culminated in degenerative changes of astroglia cells but not in overt neuronal lesions. Neither the motor deficits nor the brain lesions were aggravated by increasing the branched-chain fatty acid concentration through dietary supplementation. These data indicate that MFP-2 deficiency in mice causes a neurological phenotype in adulthood that is manifested primarily by astroglial damage.

Prenatal pseudocysts of the germinal matrix in preterm infants.

Sonographic characteristics of germinal-matrix (PGM) pseudocysts of prenatal origin detected on cranial ultrasound in preterm newborns were correlated with their outcomes. PGM cysts were classified as typical or atypical, according to their location. Typical PGM cysts were present at the head of the caudate nucleus or slightly medially, adjacent to the foramen of Monro. Cysts were defined as atypical when they were located subependymally elsewhere. Only one infant of 16 with a typical PGM cyst presented with psychomotor retardation. His cerebral scan also showed subependymal calcifications due to cytomegalovirus infection. Three babies had cysts in the frontal periventricular zones (atypical PGM cyst). They had negative cranial MRI (12-15 months of age) and normal neurological follow-up (24 months). In conclusion, isolated prenatal PGM cysts in preterm infants correlate with a normal outcome.

Subependymal caudothalamic groove hyperechogenicity and neonatal chronic lung disease.

Chronic lung disease is associated with several poorly defined risk factors for impaired cerebral development. Late neonatal onset of subependymal hyperechogenic areas in the caudothalamic groove has been reported in association with dexamethasone treatment and postnatal cytomegalovirus infection. We reviewed charts of 18 patients who developed subependymal hyperechogenicity beyond the first week of life, as well as charts of 79 patients belonging to a prospective surfactant study group. Thirteen of the 18 patients with subependymal hyperdensities had been treated with surfactant and were all found in the subgroup with chronic lung disease. In the surfactant-treated patients who did not develop chronic lung disease, we could not find any patient with subependymal hyperdensities. From the remaining five patients with ultrasound lesions, but who were not treated with surfactant, three had developed chronic lung disease. There was no evident association with dexamethasone treatment or cytomegalovirus infection. Our results support the idea of an association between chronic lung disease and the described echographic lesions in the caudothalamic groove, but the nature of the link between them is still unclear.

Two types of brain lesions in Wernicke's encephalopathy.

Analysis of 46 cases of Wernicke's encephalopathy showed that the pathological processes in the thalamus and inferior olives were clearly different from those in the mammillary bodies and the subependymal structures along the third and fourth ventricles and the aqueduct. The latter regions showed a progressive destruction of the neuropil with severe endothelial swelling and a definite sparing of the neurones. In the thalamus and inferior olives, by contrast, the reverse picture was found with neuronal disintegration, sparing of the neuropil, and a mild endothelial swelling. The disintegrating neurones in the thalamus and olives resembled those seen in anoxic necrosis. However, careful comparisons indicated a gradual drop out of the neurones in Wernicke's encephalopathy in contrast to the sudden and simultaneous affection of the neurones in anoxia. Furthermore, the nuclear structure of the affected neurones was better and longer preserved in the Wernicke lesions. The disintegrating neurones in Wernicke's disease were removed by neuronophagia and, in severe cases, the process led to a widespread neuronal loss in the thalamus and olives. The two types of histological processes largely paralleled each other in time and severity and it is suggested that they had the same aetiology.

Reaction of the hypothalamic ventricular lining following systemic administration of MSG.

Monosodium glutamate (MSG) was used to create a lesion in the CNS of the infant rat. Subcutaneous injections of MSG in four day old rat pups caused a high degree of cell necrosis in the arcuate nucleus of the hypothalamus. The tanycytic ependyma overlying this nucleus was examined at different post injection intervals with both the SEM and the TEM. Four hours following treatment the tanycytic cell bodies appear swollen and their apical surfaces have lost most of their microvilli. Within 24 hours the affected ependymal area possesses a dense population of supraependymal cells. During the following days these alterations regress so that by the 14th day of life the ependymal surface of a treated animal is indistinguishable from that of a control animal. The changes taking place in the tanycytes are compared to those occurring in astrocytes within the body of the lesion. The morphological and ultrastructural features of the supraependymal cells are considered in their similarity to those of microglia.

Lesions of the central nervous system induced in nonhuman primates by live influenza viruses.

Intracerebral and intraspinal inoculations of non-neuropathic and neuropathic strains of influenza virus into rhesus, patas and cercopithecus monkeys resulted in an acute focal ependymitis, choroiditis and meningitis followed by focal ependymal denuding without parenchymal involvement. Aqueductal stenosis and moderate hydrocephalus developed in two animals as sequelae of ependymal cell loss.