It is uncertain whether neurogenesis occurs in humans after stroke. We studied the morphologic changes that occurred in the subventricular zone (SVZ) in patients who died following an acute ischemic ...stroke.
We examined coronal brain slices from patients who died after a first-ever cerebral nonlacunar infarction in the middle cerebral artery territory. We evaluated the morphologic changes in the ipsilateral and contralateral SVZ by light and electron microscopy. Using immunochemistry with Ki-67 and PCNA, we detected cell proliferation. We used Tuj-1 for immature neurons and PSA-NCAM for migrating cells.
The study included 7 patients with a mean age of 82 +/- 5 (mean +/- SD) years; 4 were men. They died a mean of 10 +/- 5 days after the ischemic stroke. Brain samples were obtained a mean of 4 +/- 2 hours after death. In comparison with the contralateral SVZ, the following changes were observed in the ipsilateral SVZ: an increase in the width of the gap and ribbon layers, as well as in the cell density of the ribbon layer, an enlargement of the cytoplasmic volume of astrocytes, and an increase of Ki-67-positive cells. In the ipsilateral SVZ, mitoses and cells that stained for either Tuj-1 or PSA-NCAM markers were observed more frequently than in the contralateral SVZ.
We found unequivocal evidence of active cell proliferation in the ipsilateral subventricular zone following an acute ischemic stroke in our patients.
In the brain of adult rats neurogenesis persists in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus. By contrast, low proliferative activity was observed ...in the hypothalamus. We report here that, after intracerebroventricular treatment with insulin‐like growth factor I (IGF‐I), cell proliferation significantly increased in both the periventricular and the parenchymal zones of the whole hypothalamus. Neurons, astrocytes, tanycytes, microglia and endothelial cells of the local vessels were stained with the proliferative marker 5‐bromo‐2′‐deoxyuridine (BrdU) in response to IGF‐I. Conversely, we never observed BrdU‐positive ciliated cubic ependymal cells. Proliferation was intense in the subventricular area of a distinct zone of the mid third ventricle wall limited dorsally by ciliated cubic ependyma and ventrally by tanycytic ependyma. In this area, we saw a characteristic cluster of proliferating cells. This zone of the ventricular wall displayed three cell layers: ciliated ependyma, subependyma and underlying tanycytes. After IGF‐I treatment, proliferating cells were seen in the subependyma and in the layer of tanycytes. In the subependyma, proliferating glial fibrillary acidic protein‐positive astrocytes contacted the ventricle by an apical process bearing a single cilium and there were many labyrinthine extensions of the periventricular basement membranes. Both features are typical of neurogenic niches in other brain zones, suggesting that the central overlapping zone of the rat hypothalamic wall could be considered a neurogenic niche in response to IGF‐I.
There is growing evidence that SARS-CoV-2 can gain access to the central nervous system (CNS). We revise the literature on coronavirus infection of the CNS associated with neurological diseases.
...Neurological symptoms were rarely reported in the SARS-CoV and MERS-CoV epidemics, although isolated cases were described. There are also reports of cases of neurological symptoms associated with CoV-OC43 and CoV-229E infection. The presence of neurological lesions, especially demyelinating lesions in the mouse hepatitis virus model, may explain the mechanisms by which coronaviruses enter the CNS, particularly those related with the immune response. This may explain the presence of coronavirus in patients with multiple sclerosis. We review the specific characteristics of SARS-CoV-2 and address the question of whether the high number of cases may be associated with greater CNS involvement.
Although neurological symptoms are not frequent in coronavirus epidemics, the high number of patients with SARS-CoV-2 infection may explain the presence of the virus in the CNS and increase the likelihood of early- or delayed-onset neurological symptoms. Follow-up of patients affected by the SARS-CoV-2 epidemic should include careful assessment of the CNS.
Objectives
Cerebrospinal fluid (CSF) from some patients with amyotrophic lateral sclerosis (ALS) has been demonstrated to significantly reduce the neuronal viability of primary cell cultures of motor ...neurons. We aimed to study the potential clinical consequences associated with the cytotoxicity of CSF in a cohort of patients with ALS.
Methods
We collected CSF from thirty‐one patients with ALS. We analysed cytotoxicity by incubating it into the primary cultures of motor cortex neurons. Neural viability was quantified after 24 hours using the colorimetric MTT reduction assay. All patients were followed up from the moment of diagnosis to death, and a complete evaluation during disease progression and survival was performed, including gastrostomy and respiratory assistance.
Results
Twenty‐one patients (67.7%) presented a cytotoxic CSF. There were no significant differences between patients with and without cytotoxicity regarding mean time from symptom onset to the diagnosis, from the diagnosis to death, from the diagnosis to respiratory assistance with BIPAP, from diagnosis to gastrostomy and from the onset of symptoms to death. In Cox regression analysis, bulbar onset, but not cytotoxicity, gender or age at onset, was associated with a lower risk of survival.
Conclusions
Cerebrospinal fluid cytotoxicity was not associated with differential survival rates. This suggests that the presence of cytotoxicity in CSF, measured through neuronal viability in primary cultures of motor cortex neurons, could reflect different mechanisms of the disease, but it does not predict disease outcome.
Abstract Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain ...controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expression of doublecortin (DCX), a marker for immature neurons, in the dorsal DG. Ultrastructural examination of the DG region revealed disruption of progenitor cell niches several weeks after the radiation. In the first experiment, whole-brain and focal irradiation reduced DCX expression by 68% and 43%, respectively. Whole-brain and focally-irradiated rats were unimpaired compared with control rats in a matching-to-place (MTP) working memory task performed in the T-maze and in the long-term retention of the no-alternation rule. In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a “purely” contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial strategies.
Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in ...neurodegenerative diseases.
This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described.
Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases.
Myelin changes in Alexander disease Gómez-Pinedo, U; Duran-Moreno, M; Sirerol-Piquer, S ...
Neurologia (Barcelona, Spain)
33, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations ...in the gene coding for GFAP have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood.
The most widespread hypothesis is that AxD develops when a gain of function mutation causes an increase in GFAP. However, this mechanism does not explain myelin loss, given that experimental models in which GFAP expression is normal or mutated do not exhibit myelin disorders. This review analyses other possibilities that may explain this alteration, such as epigenetic or inflammatory alterations, presence of NG2 (+) - GFAP (+) cells, or post-translational modifications in GFAP that are unrelated to increased expression.
The different hypotheses analysed here may explain the myelin alteration affecting these patients, and multiple mechanisms may coexist. These theories raise the possibility of designing therapies based on these mechanisms.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases ...of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial o sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2 to 5 years after diagnosis.
In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form.
This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.
La esclerosis lateral amiotrófica (ELA) es una patología neurodegenerativa, progresiva y de etiología desconocida caracterizada por la degeneración de motoneuronas superiores e inferiores. Aproximadamente el 90% de los casos de ELA son esporádicos mientras que el 10% restante se consideran familiares. Independientemente de si son familiares o esporádicas, los pacientes desarrollan una debilidad progresiva, atrofia muscular con espasticidad y contracturas. Por lo general, la esperanza de vida en los pacientes de ELA es de 2 a 5 años.
Los modelos in vivo han ayudado a explicar la etiología y la patogénesis, así como los mecanismos de la esclerosis lateral amiotrófica. Sin embargo, estos mecanismos no están del todo esclarecidos aún, por lo que los modelos experimentales son fundamentales para continuar con el estudio de los mismos, así como para la búsqueda de posibles dianas terapéuticas. A pesar de que el 90% de los casos son esporádicos, la mayoría de los modelos utilizados hasta la actualidad para estudiar la patogénesis están basados en las mutaciones genéticas asociadas a la patología familiar, lo que provoca que la patogénesis de la ELA esporádica no sea aún conocida., Por tanto, sería fundamental el estudio de la enfermedad en modelos basados en la patología esporádica.
En el presente artículo se han revisado los principales modelos experimentales tanto genéticos como esporádicos utilizados en el estudio de esta enfermedad, enfocándonos en los que se han desarrollado utilizando el roedor como plataforma experimental.
Abstract During brain development neural stem cells may differentiate to neurons or to other cell types. The aim of this work was to assess the role of cGMP (cyclic GMP) in the modulation of ...differentiation of neural stem cells to neurons or non-neuronal cells. cGMP in brain of fetuses was reduced to 46% of controls by treating pregnant rats with nitroarginine-methylester ( l -NAME) and was restored by co-treatment with sildenafil.Reducing cGMP during brain development leads to reduced differentiation of stem cells to neurons and increased differentiation to non-neuronal cells. The number of neurons in the prefrontal cortex originated from stem cells proliferating on gestational day 14 was 715±14/mm2 in control rats and was reduced to 440±29/mm2 (61% of control) in rats treated with l -NAME. In rats exposed to l -NAME plus sildenafil, differentiation to neurons was completely normalized, reaching 683±11 neurons/mm2 . In rats exposed to sildenafil alone the number of cells labelled with bromodeoxyuridine (BrdU) and NeuN was 841±16/mm2 . In prefrontal cortex of control rats 48% of the neural stem cells proliferating in gestational day 14 differentiate to neurons, but only 24% in rats exposed to l -NAME. This was corrected by sildenafil, 40% of cells differentiate to neurons. Similar results were obtained for neurons proliferating during all developmental period. Treatment with l -NAME did not reduce the total number of cells labelled with BrdU, further supporting that l -NAME reduces selectively the differentiation of stem cells to neurons. Similar results were obtained in hippocampus. Treatment with l -NAME reduced the differentiation of neural stem cells to neurons, although the effect was milder than in prefrontal cortex. These results support that cGMP modulates the fate of neural stem cells in brain in vivo and suggest that high cGMP levels promote its differentiation to neurons while reduced cGMP levels promote differentiation to non-neuronal cells.
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