Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

Neurons in the third abdominal ganglion of the early postnatal crayfish: a quantitative and ultrastructural study.

Ultrastructural data on the third abdominal ganglion of the crayfish was heretofore only available for adult individuals. The fine structure of neurons in the adult that are involved in the escape response has been described in detail, but no similar data existed for the postnatal individual. An increase in the number of neurons in the third abdominal ganglion during postnatal stages had been reported, which suggested that several changes in the features of neurons may occur. Here we describe the general anatomy and ultrastructure of the early postnatal third abdominal ganglion, with emphasis on neurons, and we compare their characteristics to those of the adult. Abdominal ganglia of 56 crayfish of 0, 8, 10, 18, 25, 50, 110, and 150 postnatal days were processed under cacodylate buffered aldehyde fixatives, osmicated, embedded in plastic, sectioned, and examined by light and electron microscopy. The anatomy of postnatal ganglia is homologous to the anatomy of the adult ganglia except that the perineurium is not developed in postnatals. The area of neurons within the postnatal ganglion shows no stratification, but neurons are grouped in nuclei according to their size. Neurons constitute a homogeneous population in different stages of maturity, as revealed particularly by the ultrastructure of the nucleolus. Postnatal development is evident in the perineurium, which may provide structural support to the ganglion.

Glial cells of the crayfish and their relationships with neurons. An ultrastructural study.

1. Glial cells of the crayfish abdominal ganglia have been studied by transmission electron microscopy. Special attention is paid to the interrelationships between neurons and glial cells. Covers and hemocyte-related elements have also been considered. 2. Glial cells are identified by a common ultrastructure and close relationships with neurons. Four glial classes are considered, depending on their morphology, the compartment of neurons they ensheathe and neuron-glia interface. 3. Four ultrastructural classes of neurons are proposed. They differ in geometry and ultrastructure, as well as in glial covers (complexity and evaginations into the neuron somata). The morphology and organization of glial covers is specific for the neuron type they ensheathe. Specific glial covers do not differ in glia-glia communicatory structures. 4. The morphological and metabolical compartments of neurons are separated from the extracellular matrix or blood by specific glial systems. A system of two cells is interposed between neuron somata and hemolymph or the extracellular matrix. 5. Glial processes are crossed by membraneous tubular systems, at neuron perikarya and axons. Frequent gap junctions of varying area, density and number of IMP are found in the covers of neuron somata. 6. Neuron-glia interface bears numerous communicatory structures for both ionic and macromolecular exchange. They include junctions and transient modifications of membranes. Some of them suggest active transport mechanisms. 7. Modified endocytotic mechanisms seem to be responsible for the glia-to-neuron transfer of macromolecules as well as for the neuron-to-glia transfer of lamellar bodies. 8. The neuropil is divided into glomeruli (electrical or chemical) by glial processes and the trabeculae of the extracellular dense matrix. Neuron-glia membrane appositions have been found in electrical glomeruli. In chemical glomeruli, dense cored vesicles can release their content at neuron-neuron or neuron-glia intercellular cleft, at non-synaptic loci. 9. Neurons of type II contain peripheral complex Golgi systems, associated to subsurface cisternae and neuron-glia gap junctions, suggesting a cooperation of glial cells in specific macromolecular synthesis.

Morphological aspects of the ectopic granule-like cellular populations in the albino rat hippocampal formation: a Golgi study.

Rat hippocampal formation was examined by the Golgi impregnation method. Three different ectopic granule-like populations of cells were differentiated: (1) Ectopic granule-like cells of the regio inferior, located in the stratum radiatum; one or two dendrites arose from the cell body and ran towards either the molecular layer of the fascia dentata or the stratum lacunosum-moleculare of the hippocampus, where they branched into secondary and tertiary dendrites. (2) Ectopic granule-like cells of the hilar region; this cell population showed bipolar and monopolar types of dendritic tree. Unipolar cells had dendrites oriented towards the granular layer where they branched profusely. Dendritic arborisation of bipolar cells was confined to the hilus. (3) Ectopic granule-like cells of the molecular layer; they showed several structural appearances depending on their location within the layer. Axonal tracts of ectopic granule-like cells gave rise to numerous collaterals; the main branch ran to the CA4 and CA3 hippocampal subregions. Several 'en passant' and mossy-like boutons were shown along this path.

[Plasma levels of antiepileptic agents in the treatment of epilepsy]. / Estudio de los niveles plasmáticos de los antiepilépticos en el tratamiento de la epilepsia.

From a total of 560 different epileptics visited during 16 months, we have practiced 140 plasmatic dosifications of antiepileptic drugs according to EMIT technic. The antiepileptic drugs studied were: PB, DPH, PRM, VPA, CBZ and ESM. In this study only the 70 patients treated with PB in monotherapy or combined with DPH, CBZ, VPA and PRM are considered. From the 70 patients, 45 have been controlled; from them 21 (46,5%) did not reach efficient levels from anyone of the used antiepileptics. From the 70 patients 25 have been partially or bad controlled, 20 of them (80%) had PB in efficient levels, 13 (52%) had the other antiepileptic in efficient levels, 12 (47%) had both antiepileptics in efficient levels and 4 (16%) had no antiepileptic drug in efficient levels in spite of using the efficient dose in mg/Kg/day. The conclusions of this results are: we reached a good effect by using PB alone or combined under the considered efficient levels in a 46.5% of the patients; the bad controlled patients, kept on being bad controlled in spite of having 80% of them PB, the other antiepileptic or both in efficient levels.

Estudio de los niveles plasmaticos de los antiepilepticos en el tratamiento e la epilepsia. / Plasma levels of antiepileptic agents in the treatment of epilepsy

De un total de 560 epilepticos diferentes visitados en el transcurso de 16 meses, hemos practicado 140 dosificaciones plasmaticas de farmacos antiepilepticos utilizando la tecnica EMIT. Los antiepilepticos que hemos dosificado han sido: PB,DPH,PRM, VPA, CBZ y ESM. En este trabajo hemos revisado unicamente los 70 pacientes que tomaban PB en monoterapia o asociado a DPH, CBZ, VPA y PRM. De los 70 pacientes en 45 estaban controlados. De entre ellos 21 (46,5%) no llegaban a niveles eficaces de ninguno de los antiepilepticos utilizados, y sin embargo hemos conseguido un buen efecto terapeutico tanto en mono como biterapia. De estos mismos 70 pacientes, 25 estaban parcialmente o mal controlados. De entre ellos 20 (80%) tenian el PB en niveles eficaces, 13 (52%) tenian el otro antiepileptico en niveles eficaces, 12 (47%) tenian ambos antiepilepticos en niveles eficaces y 4 (16%) no tenian ningun antiepileptico en niveles eficaces a pesar de utilizar en todos, la dosis media considerada como eficaz y expresada en mg/kg/dia