Lipid profile and thyroid hormone concentrations in children with epilepsy treated with oxcarbazepine monotherapy: a prospective long-term study.

BACKGROUND AND PURPOSE: To evaluate prospectively the changes and possible associations in lipid and thyroid profiles in children treated with oxcarbazepine (OXC) monotherapy. METHODS: Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), lipoprotein (a) [Lp(a)], free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and gamma-glutamyltransferase (GGT) concentrations were measured in 23 children with epilepsy, before and at 8 and 18 months of OXC monotherapy. RESULTS: Total cholesterol was significantly increased at 8 months (P = 0.033), whereas LDL-C was significantly increased at 8 and 18 months (P < 0.001 and P = 0.004, respectively) of treatment. Lp(a) was significantly increased at 8 months (P = 0.042) and borderline significantly increased at 18 months (P = 0.050) of treatment. FT4 was significantly decreased at 8 and 18 months (P < 0.001 and P = 0.002, respectively), and TSH levels were significantly increased at 8 and 18 months (P = 0.002 and P = 0.001, respectively) of OXC monotherapy. GGT levels were significantly increased at 8 and 18 months (P < 0.001) of treatment. There were no significant alterations in HDL-C, TGs and FT3 levels during the study. Significant positive correlations were found between GGT and LDL-C levels at 8 (r = 0.468, P = 0.024) and 18 months (r = 0.498, P = 0.016), and between TSH and TC at 18 months (r = 0.508, P = 0.013) of treatment. CONCLUSIONS: OXC monotherapy may cause significant and persistent alterations in lipid and thyroid profiles in children with epilepsy. The increase in LDL-C and TC levels may be associated with liver enzymes induction and thyroid dysfunction. Further long-term prospective studies are required to confirm these findings and to determine their clinical significance.

Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy.

INTRODUCTION AND OBJECTIVES: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. MATERIAL AND METHODS: A single-group pre-posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5-7 years, with Gross Motor Function Classification System levels II-IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. RESULTS: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06±9.05; 95% confidence interval [CI], 7.40-14.71; p<0.001). CONCLUSIONS: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).

Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy. / [Artículo traducido] Mejora de la calidad de vida relacionada con la salud en niños de mediana edad con parálisis cerebral después de un alargamiento miofascial percutáneo selectivo y fisioterapia funcional.

INTRODUCTION AND OBJECTIVES: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. MATERIAL AND METHODS: A single-group pre-posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5-7 years, with Gross Motor Function Classification System levels II-IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. RESULTS: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06 ± 9.05; 95% confidence interval [CI], 7.40-14.71; p < 0.001). CONCLUSIONS: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).

PLP1 gene analysis in 88 patients with leukodystrophy.

Pelizaeus-Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty-eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation-dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array-CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array-CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.

Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy / Mejora de la calidad de vida relacionada con la salud en niños de mediana edad con parálisis cerebral después de un alargamiento miofascial percutáneo selectivo y fisioterapia funcional

Introduction and objectives: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. Material and methods: A single-group pre–posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5–7 years, with Gross Motor Function Classification System levels II–IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. Results: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06±9.05; 95% confidence interval [CI], 7.40–14.71; p<0.001). Conclusions: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).(AU)

Introducción y objetivos: Los niños con parálisis cerebral (PC) experimentan una disminución de la calidad de vida relacionada con la salud (CVRS). El objetivo de este estudio fue evaluar la CVRS de niños con PC antes y después de un programa combinado de alargamiento miofascial percutáneo selectivo (SPML) y fisioterapia funcional. Material y métodos: Se utilizó un diseño de un solo grupo con pretest y postest. Veintiséis niños de mediana edad (5 a 7 años) con PC espástica, niveles II-IV del sistema de la clasificación de la función motora gruesa se sometieron a cirugía SPML y fisioterapia de funcional posquirúrgica durante 9 meses. La versión proxy del cuestionario DISABKIDS-Smiley fue completada por uno de los padres de cada niño. Se realizaron pruebas t dependientes para comparar las puntuaciones medias previas y posteriores a la medición. Resultados: Después de 9 meses de intervención, los niños con PC tenían puntuaciones de calidad de vida significativamente más altas desde el punto de vista estadístico (diferencia de medias: 11,06±9,05; intervalo de confianza del 95%: 7,40-14,71; p <0,001). Conclusión: Este estudio demostró que los niños con PC presentaron una mejor CVRS después de un programa combinado de cirugía SPML y fisioterapia funcional.(AU)

[Artículo traducido] Mejora de la calidad de vida relacionada con la salud en niños de mediana edad con parálisis cerebral después de un alargamiento miofascial percutáneo selectivo y fisioterapia funcional / Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy

Introduction and objectives: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. Material and methods: A single-group pre–posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5–7 years, with Gross Motor Function Classification System levels II–IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. Results: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06±9.05; 95% confidence interval [CI], 7.40–14.71; p<0.001). Conclusions: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).(AU)

Introducción y objetivos: Los niños con parálisis cerebral (PC) experimentan una disminución de la calidad de vida relacionada con la salud (CVRS). El objetivo de este estudio fue evaluar la CVRS de niños con PC antes y después de un programa combinado de alargamiento miofascial percutáneo selectivo (SPML) y fisioterapia funcional. Material y métodos: Se utilizó un diseño de un solo grupo con pretest y postest. Veintiséis niños de mediana edad (5 a 7 años) con PC espástica, niveles II-IV del sistema de la clasificación de la función motora gruesa se sometieron a cirugía SPML y fisioterapia de funcional posquirúrgica durante 9 meses. La versión proxy del cuestionario DISABKIDS-Smiley fue completada por uno de los padres de cada niño. Se realizaron pruebas t dependientes para comparar las puntuaciones medias previas y posteriores a la medición. Resultados: Después de 9 meses de intervención, los niños con PC tenían puntuaciones de calidad de vida significativamente más altas desde el punto de vista estadístico (diferencia de medias: 11,06±9,05; intervalo de confianza del 95%: 7,40-14,71; p <0,001). Conclusión: Este estudio demostró que los niños con PC presentaron una mejor CVRS después de un programa combinado de cirugía SPML y fisioterapia funcional.(AU)

Discrepancy between neuroimaging findings and clinical phenotype in Alexander disease.

We present a case of infantile-onset Alexander disease (AD) with a novel glial fibrillary acidic protein mutation but without clinical evidence of neurologic deterioration. Brain MRI studies showed typical AD findings and increasing size of frontal cavitations. Serial proton MR spectroscopy demonstrated high levels of myo-inositol and lactic acid and decreasing levels of N-acetylaspartate. The degree of demyelination and the timing of the axonal degeneration may determine phenotypic severity of the disease. Conventional neuroimaging techniques cannot always predict the outcome.

Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation.

Glutaric acidemia type I (GA-I) is a treatable autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Presentation and progression of disease are variable ranging from asymptomatic carrier state to catastrophic encephalopathy. GA-I usually presents before age 18 months, usually triggered by childhood infection, with mild or severe acute encephalopathy, striatal degeneration, and movement disorder, most often acute dystonia. At a presymptomatic stage diagnosis is suggested clinically by macrocephaly, radiologically by widened Sylvian fissures and biochemically by the presence of excess 3-hydroxyglutaric acid and glutaric acid in urine. Treatment consists of lysine-restricted diet and carnitine supplementation, specific diet restrictions, as well as symptomatic and anticatabolic treatment of intercurrent illness. Presymptomatic diagnosis and treatment are essential to prognosis. We report the case of 16-year-old macrocephalic female with late-onset GA-I and unusual paucisymptomatic presentation with fainting after exercise and widespread white matter signal changes at MRI. She was compound heterozygote for a novel mutation (IVS10-2A>G) affecting splicing at GCDH and a common missense mutation (c. 1240C>T; p.Arg402Trp, R402W). Interestingly, the site of the novel mutation is the nucleotide position of a common mutation found almost exclusively in patients of Chinese/Taiwanese origin (IVS10-2A>C).

Transient features of tachykinin peptide innervation of the dorsal lateral geniculate nucleus of the rabbit during postnatal development.

The tachykinin peptide innervation of the developing dorsal lateral geniculate nucleus of the rabbit was studied with immunocytochemical techniques at the light and electron microscopic levels by using an antibody directed to the C-terminal of the mammalian tachykinin peptides. At birth, the rabbit's lateral geniculate nucleus was densely innervated by a large number of labeled fibers. These relatively unbranched axons were dispersed throughout the nucleus but showed a higher density of fiber packing in the external layer of the alpha sector. Over the next three weeks this pattern of distribution changed dramatically. Immunoreactive fibers were gradually eliminated from most of the nucleus, and, by the end of the third postnatal week, they appeared as a narrow plexus deep to the optic tract. At the same time, these axons showed major morphological alterations as they gradually became thicker and developed terminal arborizations characterized by spherical or elongated enlargements. Overall, by the end of the third postnatal week, the pattern of distribution and appearance of tachykinin-labelled fibers in the dorsal lateral geniculate nucleus were similar to those described in the adult rabbit (Brecha et al., 1987). Ultrastructural analysis has shown that during the first week, tachykinin-immunoreactive profiles appeared as round or elongated varicosities making asymmetrical synapses with dendritic shafts throughout the lateral geniculate nucleus. Thereafter, as they were progressively restricted to the external layer of the alpha sector of the nucleus, they began to form multiple synaptic contacts with neuronal processes in complex glomerular neuropil. On the basis of the present and previous findings, we suggest that tachykinin peptides not only play a role as putative neurotransmitters in the retinogeniculate pathway, but they may also play a role in the development of the lateral geniculate nucleus and of the retinogeniculate projection system in the rabbit.

Serotonergic innervation of the lateral geniculate nucleus of the rat during postnatal development: a light and electron microscopic immunocytochemical analysis.

The serotonergic innervation of the developing lateral geniculate nucleus of the rat was studied with immunocytochemical techniques at the light and electron microscope levels. A relatively small number of thick serotonergic fibers were observed at the time of birth, distributed more densely in the ventral portion of the nucleus and in the intergeniculate leaflet than in the dorsal lateral geniculate nucleus. By the end of the first postnatal week, this distribution pattern was more clearly established, but the number of immunoreactive fibers was increased. Thereafter, and until the adult pattern was established at the end of the third postnatal week, serotonergic fibers increased further in number and changed morphologically (e.g., they became finer and more ramified with closely spaced varicosities), but their pattern of distribution remained unchanged. Electron microscopical analysis of the dorsal lateral geniculate nucleus revealed that the vast majority of serotonin varicosities formed asymmetrical synapses with dendritic shafts; axosomatic synapses were a feature of the nucleus only at the time of birth. The proportion of serotonin varicosities forming synapses increased gradually from birth to reach a peak at the end of the second postnatal week, then declined markedly in the following week before increasing again at a later stage. It may be speculated that synapses formed during the first two weeks of life may be related to the involvement of serotonin in the morphogenesis of the lateral geniculate nucleus, whereas those formed later in development may be involved in the mediation of neurotransmitter effects.

Proportion of glutamate- and aspartate-immunoreactive neurons in the efferent pathways of the rat visual cortex varies according to the target.

Immunohistochemistry, with antisera directed against glutamate (Glu) or aspartate (Asp), was combined with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) histochemistry to examine the distribution, morphology, and proportions of Glu- and Asp-containing neurons that give rise to corticofugal and callosal projections of the rat visual cortex. WGA-HRP injections in the dorsal lateral geniculate nucleus resulted in retrograde labelling of small and medium-sized cells throughout layer VI of the visual cortex. Of these cells, 60% were also Glu-immunoreactive and 61% Asp-positive. WGA-HRP injections in the superior colliculus labelled large and medium-sized neurons in the upper portion of layer V of the visual cortex. Of these cells, 46% were also stained for Glu and 66% for Asp. Injections in the pontine nuclei resulted in retrograde labelling of cells in the deeper part of cortical layer V. Retrogradely labelled cells, which were also immunoreactive for Glu or Asp, were large pyramidal cells. Corticopontine neurons, which were also Glu-positive, accounted for 42% of the total number of WGA-HRP labelled cells, whilst for Asp-positive neurons this percentage was 51%. Finally, after injections in the visual cortex, retrogradely labelled small and medium-sized cells were found throughout layers II-VI in the contralateral visual cortex. Of these neurons, 38% were also labelled for Glu while 49% were also Asp-immunoreactive. The present results demonstrate that substantial proportions of projection neurons in the rat visual cortex are immunoreactive for Glu or Asp, suggesting that these excitatory amino acids are the major transmitters used by the cortical efferent systems examined. Furthermore, the proportions of these immunoreactive neurons in the efferent pathways vary according to the target.

Thalamic projections to motor, prefrontal, and somatosensory cortex in the sheep studied by means of the horseradish peroxidase retrograde transport method.

In this study the motor, prefrontal, and somatosensory areas of the sheep cerebral cortex were defined on the basis of their thalamic afferents traced with the horseradish peroxidase method. The motor area (areas 4 and 6) occupies the cruciate gyrus. It receives a substantial projection from the thalamic nuclei ventralis anterior, ventralis lateralis, medialis dorsalis, and centralis lateralis and a smaller one from the nuclei ventralis medialis, centralis medialis, paracentralis, lateralis dorsalis, lateralis posterior, centromedianus, parafascicularis, suprageniculatus, ventralis posterolateralis, and the midline nuclei. Area 4 receives afferents mainly from the nuclei ventralis anterior, ventralis lateralis, medialis dorsalis, and lateralis posterior, whereas area 6 receives afferents mainly from the nuclei ventralis anterior, medialis dorsalis, and lateralis posterior and fewer afferents from the nucleus ventralis medialis. The prefrontal area occupies the gyrus proreus and receives numerous afferents from the nucleus medialis dorsalis and fewer from the nuclei lateralis posterior and ventralis medialis. The area extending between the lateral fissure, the coronal sulcus, the presylvian sulcus, and the rostral branch of the lateral fissure is connected mainly with sensory thalamic nuclei. Thalamic afferents were found to emanate from the nuclei ventralis posteromedialis (its parvicellular part included), ventralis posterolateralis, ventralis medialis, paracentralis, lateralis posterior, medialis dorsalis, centromedianus, suprageniculatus, paraventricularis, the substantia nigra, and the ventral part of the lateral geniculate nucleus. The first somatosensory area (Johnson et al., '74, J. Comp. Neurol. 158:81-108) was found to extend between the coronal, the diagonal, and the anterior suprasylvian sulci and to receive afferents almost exclusively from the nucleus ventralis posteromedialis.

Somatostatinlike immunoreactive neurons in the hedgehog (Erinaceus europaeus) and the sheep (Ovis aries) central nervous system.

The morphology and distribution of somatostatinlike immunoreactive perikarya in the central nervous system of the hedgehog and sheep have been studied by means of the peroxidase-antiperoxidase immunohistochemical method. Intracerebroventricular colchicine infusion not only enhanced the immunostaining but also revealed new immunoreactive cell bodies. In both hedgehog and sheep immunoreactive neurons of various forms, ranging from 12 to 28 microns in diameter, were observed in a number of homologous brain structures. However, some species-related differences were noticed. Thus, somatostatinlike immunoreactive neurons were found only in the hedgehog anterior olfactory nucleus, olfactory tubercle, nucleus accumbens, medial parabrachial nucleus, raphe nuclei of the medulla, and spinal trigeminal nucleus, whereas some somatostatin-positive neurons were observed in the locus coeruleus and the pontine reticular formation of the sheep only. Mapping of peptides in species like sheep and hedgehog, with basically different orientations of living behaviour, may contribute in strengthening or extending our views concerning the role of peptides in the central nervous system of mammals.

Neurotensinlike immunoreactive neurons in the hedgehog (Erinaceus europaeus) and the sheep (Ovis aries) central nervous system.

Neurotensin-containing neurons in the hedgehog and sheep central nervous system were studied immunohistochemically. In both species, mapping of neurotensin neurons was achieved only after pretreatment with colchicine injected intracerebroventricularly 2 days prior to perfusion. Bipolar or multipolar neurotensin neurons, 10-30 micron in diameter, were observed in the following regions of the central nervous system of both species: medial amygdaloid nucleus, lateral septal nucleus, interstitial nucleus of the stria terminals, caudate nucleus, preoptic area, and hypothalamus. On the contrary, while immunoreactive neurons were found in the central amygdaloid nucleus, nucleus accumbens, nucleus of the diagonal band, subthalamus, superior central nucleus, dorsal raphe nucleus, central gray substance of the pons, and dorsal horn of the spinal cord of the hedgehog, respective regions of the sheep appeared to be devoid of immunoreactive perikarya. Also, in some regions, namely the hippocampal formation, the central gray substance of the midbrain, the locus coeruleus, and the nucleus of the solitary tract, neurotensin neurons were found exclusively in the latter species. The existence of these differences in the distribution pattern of neurotensin-immunoreactive neurons between the two species as well as between them and others already examined is briefly discussed.

VIP- and CCK-like-immunoreactive neurons in the hedgehog (Erinaceus europaeus) and sheep (Ovis aries) brain.

The distribution pattern and the morphology of vasoactive intestinal polypeptide (VIP)- and cholecystokinin (CCK)-like-immunoreactive neurons were studied in the brain of the hedgehog and the sheep by means of the peroxidase-antiperoxidase immunocytochemical method. A total of 34 hedgehogs and 26 sheep of both sexes were used. Fourteen hedgehogs and 13 sheep received an intracerebroventricular injection of colchicine that enhanced the immunostaining and revealed "new" immunoreactive cell bodies. VIP-immunoreactive bipolar and multipolar neurons were observed in both species in the cerebral cortex, hippocampal formation, amygdaloid complex, hypothalamus, and central gray substance of the midbrain. CCK-immunoreactive bipolar, bitufted, and multipolar neurons displayed a broader distribution in both mammals than VIP neurons and were found in the cerebral cortex, the hippocampal formation, the amygdaloid complex, the hypothalamus, the mesencephalon, and the pons. In the cortex, in both the hedgehog and the sheep, VIP neurons were located in all layers but were concentrated in layers II and III, with the majority being typical bipolar. CCK neurons were more numerous in the superficial layers (I-III) but were found in the deep layers as well. They were bipolar, bitufted, or multipolar in morphology. From these neurons a small percentage, which were located almost exclusively in layers II and III of the visual cortex, exhibited also VIP immunoreactivity. Perikarya of such double-labeled cells were ovoid or round in shape with one or two main processes emanating from each pole of the cell body and oriented perpendicularly to the pia. The coexistence of the two peptides within individual neurons of the cortex has not been reported in other species and its physiological significance is discussed in relation to the GABAergic neurons of the cortex.

Morphology of neurons in the basal forebrain nuclei of the rat: a Golgi study.

The neuronal cell types and their morphology in the nucleus basalis (NB), in the horizontal and vertical limbs of the diagonal band of Broca (NHL and NVL), and in the medial septal nucleus (MSN) were examined in Golgi-impregnated material. Cells appeared as multipolar or oligopolar and displayed a variable dendritic morphology; their somata varied considerably both in shape and size. The dendrites of most cells were restricted within nuclear boundaries, although occasionally neurons located near boundaries, particularly cells in NHL, extended dendritic arbors into neighboring areas. Axons were rarely seen, but when they were found they were generally not impregnated beyond the initial segment and displayed no apparent preferential direction. Three types of cells common to each of the 4 nuclear groups could be identified on the basis of soma shape and dendritic form. The first type included large multipolar neurons with triangular or polygonal perikarya and typically 3-5 dendrites emerging from the poles of each cell. These cells were especially numerous in NB, NHL, and NVL, but were much less frequent in MSN. The second type comprised medium-sized cells with round or oval somata and a small number, usually 2-3, of dendrites. They constituted a large percentage of the cell population in MSN, but were also encountered in NHL and NVL as well as in NB. The third type consisted of cells with fusiform or spindle-shaped somata with usually single dendrites emanating from each pole of the cell. A rare but distinct type of spindle-shaped neuron with dendrites bearing a rich complement of long and thin appendages was observed mainly in the ventral border of NHL. The present observations suggest that although the proportions and sizes of the 3 types of neurons vary between the 4 nuclei, neurons throughout the basal forebrain share common morphological characteristics.

Claustrum in the hedgehog (Erinaceus europaeus) brain: cytoarchitecture and connections with cortical and subcortical structures.

The cytoarchitecture of the claustrum in the hedgehog (Erinaceus europaeus) brain, the morphology of its neurons, and the efferent connections with cortical and subcortical structures were studied with the Nissl and Klüver-Barrera, the Golgi, and the horseradish peroxidase methods. It was found that the claustrum is a well developed nucleus in the hedgehog telencephalon and, as in other mammals, is divided into dorsal and ventral parts. In Golgi-stained sections, spiny multipolar cells are the predominant neurons of both the dorsal and the ventral claustrum and are projection neurons. Aspiny multipolar neurons with fewer, often beaded, dendrites constitute a minority in both divisions and are interneurons. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the prefrontal, motor, somatosensory, auditory and visual areas, and HRP or WGA-HRP injections in the thalamus showed that: (1) the claustroneocortical projections originate in the dorsal claustrum and are distributed to the entire neocortex; these projections are mainly ipsilateral but some also originate contralaterally; (2) the claustroneocortical projections show a rough topographic organization; there exists a substantial degree of overlap; and (3) the claustrothalamic projection, arising throughout the dorsal claustrum, is strictly ipsilateral. No evidence of a thalamoclaustral projection was found. The present results suggest that, although the hedgehog has been referred to as a "paleocortical mammal" owing to the great development of its rhinencephalic structures in comparison with its small neocortex, the dorsal claustrum is well developed and is connected with all neocortical areas as well as with the thalamus, establishing it as a key structure in the hedgehog forebrain.

Serotonergic innervation of the mature and developing lateral septum of the rat: a light and electron microscopic immunocytochemical analysis.

The serotonergic innervation of the adult and developing lateral septum of the rat was studied with immunocytochemical techniques at the light and electron microscopic levels. A few, relatively thick serotonergic fibres are found in the lateral septum at the time of birth, but they are restricted to its medial part. They subsequently extend towards the lateral ventricle, increase in number and attain their final distribution pattern by the end of the first postnatal week. Thereafter they become finer, with regularly spaced varicosities, show a higher density, and generally exhibit features, density, and pattern of innervation comparable to the adult at the end of the third postnatal week. In the dorsal portion of the lateral septum, serotonergic fibres form characteristic pericellular basket-like arrangements around cell somata and their primary dendrites. These baskets are first observed at P7, and subsequently increase both in number and in terms of the number of serotonergic terminals which they comprise. The present findings suggest that the development of serotonergic innervation of the lateral septum parallels the neuronal differentiation in this area. Ultrastructural analysis has shown that the vast majority (congruent to 95%) of serotonin varicosities make symmetrical synapses with somata, dendritic shafts and spines. These varicosities in new-born animals are in close association with neuronal elements, without any intervening neuroglial processes, but towards the end of the first postnatal week they exhibit well-defined synaptic specializations. The mean diameter of serotonergic varicosities making synapses does not change substantially with age. Serotonin-receptive neurons have several morphological features in common with the type I cells described in a previous Golgi study of the lateral septum [Alonso and Frotscher (1989) J. comp. Neurol. 286, 472-487]. Some speculations on the chemical identity of the serotonin-receptive cells have been put forward in the present study but double-labelling studies will certainly shed more light on the organization of the serotonergic innervation of the lateral septum.

Postnatal development of the dopaminergic system of the striatum in the rat.

The dopaminergic innervation of the developing caudate-putamen (patches and matrix) and nucleus accumbens (shell and core) of the rat was examined with light and electron microscope immunocytochemistry, using antibodies against dopamine. Light microscopic analysis showed, in accordance with previous studies, that early in life, dopaminergic fibers were relatively thick and present throughout the striatum. Their distribution was heterogeneous, showing dense aggregations, the so-called dopamine islands. The pattern of innervation became more uniform during the third postnatal week with most of the dopamine islands no longer detectable. For electron microscopic analysis, parts of the caudate-putamen containing dopamine islands or matrix, and of the nucleus accumbens, from the shell and the core of the nucleus, were selected. This analysis revealed that symmetrical synapses between immunoreactive profiles and unlabeled dendritic shafts predominated throughout development but, at the late stages, symmetrical axospinous synapses also became a prominent feature. These findings indicate that: (1) although the caudate-putamen and the nucleus accumbens have different connections and functions, they exhibit similar types of dopaminergic synapses, and (2) the relatively late detection of dopaminergic axospinous synapses suggests that the development of the dopaminergic system in the striatum is an active process, which parallels the morphological changes of striatal neurons and may contribute to their maturation.

The development of neurons in the nuclei of the horizontal and vertical limb of the diagonal band of Broca of the rat: a qualitative and quantitative analysis of Golgi preparations.

We have studied the morphological alterations of neurons in the nuclei of the horizontal (NHL) and vertical (NVL) limbs of the diagonal band of Broca of rats from late embryonic life to maturity using the Golgi-Stensaas and Golgi-Cox methods. During late embryonic life and in the first postnatal days, the two nuclei of the diagonal band of Broca were found to be located near the ventral surface of the brain. Shortly thereafter, neurons in the NHL and NVL gradually take up the positions which they normally occupy in adulthood. At this stage neurons were small with round or elongated somata and 1-3 primary dendrites that only occasionally bore spines and very seldom showed varicosities, features commonly shown by neurons at later postnatal ages. At birth, cells showing varying soma shapes and dendritic morphology were present, and by postnatal day 4 (P4) the three forms of neurons previously described in adult rats (Dinopoulos et al., J. Comp. Neurol., 272 (1988) 461-474) were readily distinguished. During the second postnatal week, the size of cell somata as well as the number, size and extent of dendritic branching underwent considerable increases in both nuclei and at P14 neurons showed features typical of their adult counterparts. In addition they showed a dramatic increase in the number of spines which was followed during the next 10 days by a substantial decrease. Overall, the dendritic geometry of neurons in the NHL and NVL did not change significantly after P14, although their cell bodies continued to increase in size until the middle of the fourth and fifth postnatal weeks respectively. These findings suggest that neurons in the nuclei of the diagonal band of Broca show continuous growth from embryonic life to the end of the second postnatal week when they acquire morphological features comparable to the adult. Thereafter they exhibit only minor morphological alterations with the exception of extensive spine elimination which is pronounced during the third postnatal week and continues until adulthood.