Incidence of asthma in young adults from Castellon, Spain: A prospective cohort study.

BACKGROUND: The objective was to estimate the incidence of asthma in young adults from 13-15 years old to 23-25 years old, and associated factors. METHODS: In 2012, a population-based prospective cohort study was carried out in Castellon from the cohort who had participated in the International Study of Asthma and Allergy in Childhood in 1994 and 2002. A telephone survey was undertaken using the same questionnaires. A new case of asthma was defined as a participant free of the disease in 2002 who suffered asthma, was diagnosed with asthma, or took medications against asthma based on self-report from 2002 to 2012. RESULTS: The mean age of participants was 24.9±0.6 with a follow-up of 79.1%. Asthma cumulative incidence was 3.4%: 44 new cases occurred among 1280 participants. The incidence was higher in females than males with relative risk (RR)=2.02 (95% confidence interval [CI] 1.1-3.8). A significant decrease of asthma incidence density was observed (8.2 cases to 3.5 cases per 1000 person/year). Factors associated with the incidence of asthma were allergic rhinitis (RR=4.05; 95% CI 1.7-9.6), bronchitis (RR=2.13; 95% CI 1.0-4.5), mother's age at time of birth (RR=0.87; 95% CI 0.8-0.9) and a pet other than a dog or cat (RR=0.42; 95% CI 0.2-0.9). For gender, some variations in the risk factors were observed. CONCLUSIONS: A significant decrease in the incidence of asthma was observed. Several risk and protective factors were found.

Incidence of allergic rhinitis in a cohort of young adults from 13-15 years old to 23-25 years old in Castellon (Spain).

BACKGROUND: The objective of this study was to estimate the incidence of Allergic Rhinitis (AR) in young adults and its risk or protective factors. METHODS: A population-based prospective cohort study was carried out in 2012. The cohort participated in the International Study of Asthma and Allergy in Childhood in Castellon in 1994 and 2002. A telephone survey was conducted using the same questionnaires. A new case of AR was defined as the participants free of the disease in 2002, who self-reported suffering from AR or taking medications for AR in the period 2002-2012. RESULTS: Of the 1805 schoolchildren in the cohort in 2002, 1435 young adults (23-25 years old) participated (follow-up 79.1%) in 2012; 743 were female and 692 male; their mean age was 24.9±0.6 years. Two hundred new cases of AR occurred in 1259 participants free of the disease with an incidence of 17.3 per 1000 person-years, and the incidence increased from 2002 (RR=1.42; 95% CI 1.15-1.75). The risk factors of AR adjusted by age and gender were sinusitis (RR=1.77; 95% CI 1.16-2.68), atopic dermatitis (RR=1.51; 95% CI 1.11-2.06) and constant exposure to truck traffic (RR=1.88; 95% CI 1.12-3.17). For male participants, the risk factors were asthma, sinusitis and atopic dermatitis, and for females bronchitis was a risk factor and presence of older siblings a protective factor. CONCLUSIONS: An increase in AR incidence was observed. Sinusitis, atopic dermatitis and constant exposure to truck traffic were the risk factors of the AR with some differences by gender.

Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington disease.

Substitutive therapy using fetal striatal grafts in animal models of Huntington disease (HD) have already demonstrated obvious beneficial effects on motor indices. Using a new phenotypic model of HD recently designed in primates, we demonstrate here complete and persistent recovery in a frontal-type cognitive task two to five months after intrastriatal allografting. The striatal allografts also reduce the occurrence of dystonia, a major abnormal movement associated with HD. These results show the capacity of fetal neurons to provide a renewed substrate for both cognitive and motor systems in the lesioned adult brain. They also support the use of neural transplantation as a potential therapy for HD.

Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized controlled trial.

The objective of this study was to assess the effectiveness of photobiomodulation with low-level laser therapy (LLLT) as a preventive and therapeutic procedure for the treatment of oral and oropharyngeal mucositis caused by radio-chemotherapy in patients diagnosed with oral squamous cell carcinoma (SCC). An experimental, prospective, double-blind, randomized controlled study was conducted involving patients diagnosed with oral SCC undergoing oncological treatment. The variables analyzed included grade, appearance, and remission of mucositis. A final sample of 26 patients was included: 11 (42.3%) in the study group and 15 (57.7%) in the control group; their average age was 60.89±9.99years. Statistically significant differences between the groups were observed from week 5 of oncological treatment; 72.7% of the laser group showed normal mucosa (mucositis grade 0), while in the control group, 20.0% showed grade 0 mucositis and 40.0% showed grade 2 mucositis (P<0.01). No statistically significant difference between the groups was found regarding the application or use of medication throughout the study period (P>0.05). The tolerance evaluation did not show any statistically significant difference between the groups regarding the occurrence of side effects or adverse events during the trial (P>0.05). Photobiomodulation with LLLT reduces the incidence and severity of mucositis in patients treated with radiotherapy±chemotherapy.

Hydrogeochemical characterization of a shallow alluvial aquifer: 1 baseline for groundwater quality assessment and resource management.

Considering the progressive depletion of groundwater quantity and the alteration of superficial and groundwater quality in the Madrid region, a highly populated area with extended urbanizations in the north and agricultural activities in the south, we conducted a monitoring study over a period of 2.5 years (2015-2017). The study was conducted in the Jarama-Tajuña shallow alluvial aquifer system located southeast of Madrid, where the exploitation of the aquifer and the Jarama river have increased exponentially in the last decade being affected by both urban and agricultural activities. Our aims were to provide: i) a geochemical characterization of the surface and groundwater properties; ii) identify the process responsible for the geochemical evolution and mineralization of the waters; iii) assess the water quality (i.e. nitrates, ammonia, sodium and chloride as potential contaminants) and the water suitability for irrigation (SAR, Wilcox, KI and MH indexes); and iv) identify the main sources of contamination in the area. A set of plots, ion ratios, correlation coefficients, multivariate statistical analyses and indexes were performed. Results indicated that rock weathering largely controls the hydrogeochemistry of the system and that wastewater treatment plant discharges and agricultural practices significantly affect the composition of the water, causing an important decline of both surface and groundwater chemical quality. Nonetheless, water suitability for irrigation is admissible. Thus, taking additional measures to increase its quality are not necessary. With this study we aimed to establish a base line to evaluate future changes in the groundwater properties from the Madrid region enabling the planners and policy makers to develop a strategy to mitigate the impact of the exponential increase of urban and agriculture activities on groundwater resources.

Learning and memory dissociation in rats with lesions to the subthalamic nucleus or to the dorsal striatum.

The striatum and the subthalamic nucleus (STN) are the two main cortical inputs to the basal ganglia. Both structures are involved in motor and cognitive functions, particularly executive functions, known to rely mainly on fronto-basal ganglia circuits. The present work investigated the respective role of the dorsal part of the striatum (dST) and the STN by studying their involvement in learning and memory processes in two separate experiments. In a first experiment, rats with lesions to the STN or to the dST were trained in a light-tone discrimination task. When the learning criterion was reached, rats were then trained to the reversed discrimination. In a second experiment, surgery was done when the learning criterion had been reached. Three weeks after surgery, animals were then subjected to two relearning sessions and then to either a reversal learning or a working memory task. When surgery was done before learning, dysfunction of the dorsal striatum induced slight difficulties in acquisition, whereas dysfunction of the STN induced no difficulties during the initial learning but induced a more rapid inhibition of responses to the first lever press following the presentation of the tone during the reversed discrimination. In the second experiment, dST-lesioned rats showed long-term memory deficit in contrast to STN-lesioned rats which showed no difficulties during relearning but deficits in working memory. These results indicate a clear dissociation in cognitive functions in which STN and dorsal striatum are involved, suggesting that the fronto-striatal circuit and the fronto-STN circuit support, at least in part, different cognitive functions.

Acceleration of apatite nucleation on microrough bioactive titanium for bone-replacing implants.

The viability of a new two-step method for obtaining bioactive microrough titanium surfaces for bone replacing implants has been evaluated. The method consists of (1) Grit blasting on titanium surface to roughen it; and (2) Thermo-chemical treating to obtain a bioactive surface with bone-bonding ability by means of nucleating and growing an apatite layer on the treated surface of the metal. The aim of this work is to evaluate the effect of surface roughness and chemical composition of the grit-blasting particles on the ability of the surfaces of nucleating and growing a homogeneous apatite layer. The determination and kinetics of the nucleation and growing of the apatite layer on the surfaces has mainly been studied with environmental scanning electron microscopy (ESEM) and grazing-incidence X-ray diffractometry. The results show that Al(2)O(3)-blasted and thermochemically-treated titanium surfaces accelerates nucleation of the apatite, whereas SiC-blasted and thermochemically-treated titanium surfaces inhibits apatite nucleation, compared with the well studied polished and thermochemically-treated titanium surfaces. The acceleration of the apatite nucleation on the Al(2)O(3)-blasted microrough titanium surfaces is because concave parts of the microroughness that are obtained during grit blasting provides to the rough and bioactive surfaces with a chemical- and electrostatic-favored situation for apatite nucleation. This consists of a high density of surface negative charges (also assisted by the nanoroughness of the surface obtained after the thermochemical treatment) and an increased concentration of the Ca(2+)-ions of the fluid, which have a limited mobility at the bottom of the concave parts.

Vitreous SiO2-CaO coatings on Ti6Al4V alloys: reactivity in simulated body fluid versus osteoblast cell culture.

Vitreous coatings of the SiO(2)-CaO system have been prepared on Ti6Al4V substrates by the sol-gel method. The textural parameters (porosity and roughness) and thickness of the films obtained increase when the concentration of the precursor solutions is raised. In vitro studies of these coatings have been performed using two approaches: soaking in simulated body fluid, and by growing osteoblasts on these materials. The results of both studies show differences in terms of chemical reactivity. While in simulated body fluid the coatings were dissolved without forming a bioactive surface, when osteoblast-like cells grew on the coatings they were more stable. Furthermore, cell culture assays show biocompatible behavior of these coatings making them of potential interest for clinical applications. The effect of the textural parameters of the obtained coatings on the cell functions (attachment, spreading, proliferation and differentiation) has also been studied. The results show an increase in these cell parameters as the roughness and porosity of the coatings increase.

Replicating Huntington's disease phenotype in experimental animals.

Huntington's disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder characterized by involuntary choreiform movements, cognitive decline and a progressive neuronal degeneration primarily affecting the striatum. There is at present no effective therapy against this disorder. The gene responsible for the disease (IT15) has been cloned and the molecular defect identified as an expanded polyglutamine tract in the N-terminal region of a protein of unknown function, named huntingtin (The Huntington's Disease Collaborative Research Group, 1993. Cell 72, 971-983). An intense, search for the cell pathology attached to this molecular defect is currently under way [see Sharp and Ross (1996, Neurobiol. Dis. 3, 3-15) for review]. Huntingtin interacts with a number of proteins, some of which have well identified functions, and it has thus been suggested that alterations in glycolysis, vesicle trafficking or apoptosis play a role in the physiopathology of HD. On the other hand data derived from positron emission tomography (PET), magnetic resonance spectroscopy and post-mortem biochemical evidence for a defect in succinate oxidation have suggested the implication of a primary impairment of mitochondrial energy metabolism. All these hypotheses are not necessarily to be opposed and recent findings indicate that the HD mutation could possibly directly alter mitochondrial functions which would in turn activate apoptotic pathways. To test this mitochondrial hypothesis, we studied the effects in rodents and non-human primates of a chronic blockade of succinate oxidation by systemic administration of the mitochondrial toxin 3-nitropropionic acid (3NP). Extensive behavioural and neuropathological evaluations showed that a partial but prolonged energy impairment induced by 3NP is sufficient to replicate most of the clinical and pathophysiological hallmarks of HD, including spontaneous choreiform and dystonic movements, frontal-type cognitive deficits, and progressive heterogeneous striatal degeneration at least partially by apoptosis. 3NP produces the preferential degeneration of the medium-sized spiny GABAergic neurons with a relative sparing of interneurons and afferents, as was observed in HD striatum. The present manuscript reviews the different aspects of this neurotoxic treatment in rodents and non-human primates, and its interest as a phenotypic model of HD to understand the degenerative process of HD and test new therapeutic strategies.

[Cranial hemophilic pseudotumor]. / Pseudotumor hemofílico craneal. Caso clínico.

The haemophilic pseudotumor is defined as an encased hematoma that increases of volume progressively by episodes of recurrent hemorrhage. It is a rare complication of haemophilia occurring in 1-2% of patients with moderate or severe factor VIII or IX deficiency. Its more frequent location is in the long bones of low extremities and pelvis. We report a case of a 21-year-old man with moderate deficiency of factor VIII (19% of normal factor VIII activity) that developed a pseudotumor in the cranium. To our knowledge, this is the third case of the cranial hemophilic pseudotumor in medical literature.

Comparative study between prokaryotes and eukaryotes by chemical iodination of ribosomal proteins.

Escherichia coli and Saccharomyces cerevisiae ribosomal proteins were chemically iodinated with 125I by chloramine T under conditions in which the proteins were denatured. The labelled proteins were subsequently separated by two-dimensional gel electrophoresis with an excess of untreated ribosomal proteins from the same species. The iodination did not change the electrophoretic mobility of the proteins as shown by the pattern of spots in the stained gel slabs and their autoradiography. The 125I radioactivity incorporated in the proteins was estimated by cutting out the gel spots from the two-dimensional electrophoresis gel slabs. The highest content of 125I was found in the ribosomal proteins L2, L11, L13, L20/S12, S4 and S9 from E. coli, and L2/L3, L4/L6/S7, L5, L19/L20, L22/S17, L29/S27, L35/L37 and S14/S15 from S. cerevisiae. Comparisons between the electrophoretic patterns of E. coli and S. cerevisiae ribosomal proteins were carried out by coelectrophoresis of labelled and unlabelled proteins from both species. E. coli ribosomal proteins L5, L11, L20, S2, S3 and S15/S16 were found to overlap with L15, L11/L16, L36/L37, S3, S10 and S33 from S. cerevisiae, respectively. Similar coelectrophoresis of E. coli 125I-labelled proteins with unlabelled rat liver and wheat germ ribosomal proteins showed the former to overlap with proteins L1, L11, L14, L16, L19, L20 and the latter with L2, L5, L6, L15, L17 from E. coli.

The effects of air pollution and meteorological parameters on respiratory morbidity during the summer in São Paulo City.

Effects of meteorological variables and air pollutants on child respiratory morbidity are investigated during two consecutive summers (December-March 1992/1993 and 1993/1994) at the Metropolitan Area of São Paulo (MASP), Brazil. The MASP, with almost 17 million inhabitants, is considered the most populous region in South America. Due to warmer temperatures, increased rainfall and consequent low levels of air pollutants during the summer compared to winter, less attention has been paid to epidemiological studies during this season, especially in tropical urban areas such as São Paulo. In the present work, principal component analysis (PCA) is applied to medical end environmental data to identify patterns relating child morbidity, meteorological variables and air pollutants during the summer. The following pollutant concentrations are examined: SO2, inhalable particulate matter (PM10), and O3. The meteorological variables investigated are air temperature, water vapor (water vapor density) and solar radiation. Although low correlation between respiratory morbidity and environmental variables are, in general, observed for the entire dataset, the PCA method indicates that child morbidity is positively associated with O3 for the 1992/1993 summer. This pattern is identified in the third principal component (PC3), which explains about 19% of the total variance of all data in this summer. However, the 1993/1994 summer shows a more complex association between both groups, suggesting stronger ties with meteorological variables. Marked changes in synoptic conditions from the end of January to end of March of the 1993/1994 summer seem to have played an important role in modulating respiratory morbidity. A detailed examination of meteorological conditions in that period indicates that prefrontal (postfrontal), hot (cold) and dry (wet) days favored the observed decrease (increase) of respiratory morbidity.

Restoration of cognitive and motor functions by ciliary neurotrophic factor in a primate model of Huntington's disease.

Huntington's disease (HD) is an inherited disorder characterized by cognitive impairments, motor deficits, and progressive dementia. These symptoms result from progressive neurodegenerative changes mainly affecting the neostriatum. This pathology is fatal in 10 to 20 years and there is currently no treatment for HD. Early in the course of the disease, initial clinical manifestations are due to striatal neuronal dysfunction, which is later followed by massive neuronal death. A major therapeutic objective is therefore to reverse striatal dysfunction prior to cell death. Using a primate model reproducing the clinical features and the progressive neuronal degeneration typical of HD, we tested the therapeutic effects of direct intrastriatal infusion of ciliary neurotrophic factor (CNTF). To achieve a continuous delivery of CNTF over the full period of evaluation, we took advantage of the macroencapsulation technique. Baby hamster kidney (BHK) cells previously engineered to produce human CNTF were encapsulated into semipermeable membranes and implanted bilaterally into striata. We show here that intracerebral delivery of low doses of CNTF at the onset of symptoms not only protects neurons from degeneration but also restores neostriatal functions. CNTF-treated primates recovered, in particular, cognitive and motor functions dependent on the anatomofunctional integrity of frontostriatal pathways that were distinctively altered in this HD model. These results support the hypothesis that CNTF infusion into the striatum of HD patients not only could block the degeneration of neurons but also alleviated motor and cognitive symptoms associated with persistent neuronal dysfunction.

Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid.

N-acetylaspartate (NAA) quantification by 1H-magnetic resonance spectroscopy has been commonly used to assess in vivo neuronal loss in neurodegenerative disorders. Here. the authors used ex vivo and in vivo 1H-magnetic resonance spectroscopy in rat and primate models of progressive striatal degeneration induced by the mitochondrial toxin 3-nitropropionate (3NP) to determine whether early NAA depletions could also be associated with neuronal dysfunction. In rats that were treated for 3 days with 3NP and had motor symptoms, the authors found a significant decrease in NAA concentrations, specifically restricted to the striatum. No cell loss or dying cells were found at this stage in these animals. After 5 days of 3NP treatment, a further decrease in striatal NAA concentrations was observed in association with the occurrence of dying neurons in the dorsolateral striatum. In 3NP-treated primates, a similar striatal-selective and early decrease in NAA concentrations was observed after only a few weeks of neurotoxic treatment, without any sign of ongoing cell death. This early decrease in striatal NAA was partially reversed after 4 weeks of 3NP withdrawal. These results demonstrate that early NAA depletions reflect a reversible state of neuronal dysfunction preceding cell degeneration and suggest that in vivo quantification of NAA 1H-magnetic resonance spectroscopy may become a valuable tool for assessing early neuronal dysfunction and the effects of potential neuroprotective therapies in neurodegenerative disorders.

Anatomic and biochemical correlates of the dopamine transporter ligand 11C-PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-L-dopa.

Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B'max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B'max = 26 and 36 pmol/mL) and reserpine-treated animals (B'max = 338 and 483 pmol/mL). In vivo 11C-PE2I B'max values correlated with 18F-Dopa Ki values and in vitro 125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.

Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents.

In order to compare the frontal cortex of rat and macaque monkey, cortical and subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the rat were analyzed with fluorescent retrograde tracers. In addition to afferent inputs common to the whole MFC, each subdivision of the MFC has a specific pattern of afferent connections. The dorsally situated precentral medial area (PrCm) was the only area to receive inputs from the somatosensory cortex. The specific pattern of afferents common to the ventrally situated prelimbic (PL) and infralimbic (IL) areas included projections from the agranular insular cortex, the entorhinal and piriform cortices, the CA1-CA2 fields of the hippocampus, the subiculum, the endopiriform nucleus, the amygdalopiriform transition, the amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In all these structures, the number of retrogradely labeled cells was larger when the injection site was located in area IL. The dorsal part of the anterior cingulate area (ACd) seemed to be connectionally intermediate between the adjacent areas PrCm and PL; it receives neither the somatosensory inputs characteristic of area PrCm nor the afferents characteristic of areas PL and IL, with the exception of the afferents from the caudal part of the retrosplenial cortex. A comparison of the pattern of afferent and efferent connections of the rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd areas share some properties with the macaque premotor cortex, whereas PL and IL areas may have characteristics in common with the cingulate or with medial areas 24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques.

Local circuit neurons immunoreactive for calretinin, calbindin D-28k or parvalbumin in monkey prefrontal cortex: distribution and morphology.

In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in but normal and disease states.

Studies of the IgM and IgA contamination obtained by eluting IgG from protein A-Sepharose column with pH steps.

The IgG fraction obtained from pooled human plasma by eluting a protein A column with a buffer at pH 2.5 was contaminated with approximately 30% of the IgM originally present in the sample. Both the IgM and the IgA contamination can be reduced and the IgG recovery maintained at 90% of the bound IgG when elution of the column is performed at pH 4.0

The rubro-olivary tract in the cat, as demonstrated with the method of retrograde transport of horseradish peroxidase.

The rubro-olivary projection in the cat was investigated by means of the retrograde transport of horseradish peroxidase. After injections in the inferior olive, more than a thousand labelled neurons were found in the ipsilateral red nucleus. These neurons had triangular-shaped cell bodies with an average diameter of 26.4 +/- 7.7 microns (mean +/- S.E.M.) and had few dendrites. Between 85% and 95% of the rubro-olivary neurons were found in the rostral third of the red nucleus (between A 5.5 and A 7). Morphologically, the rubro-olivary neurons are similar to rubro-thalamic neurons. Previous studies with retrograde transport of horseradish peroxidase have failed to demonstrate an extensive projection from the red nucleus to the inferior olive. These results are discussed in relation to our own findings.

Major strain differences in response to chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid in rats: implications for neuroprotection studies.

Chronic systemic treatment with 3-nitropropionic acid in rats produces persistent dystonia and bradykinesia, and striatal lesions reminiscent of Huntington's disease. However, the interpretation of results obtained with this model are complicated by a heterogeneous distribution of the response to a given toxic dose of 3-nitropropionic acid: approximately half of the animals develop selective striatal lesions, which in certain cases are associated with extrastriatal lesions, and the other half are apparently spared. Thus, the chronic 3-nitropropionic acid lesion model can be difficult for neuroprotection studies in which a consistent response to neurotoxic treatment is prerequisite. We hypothesized that some of the variability in the model was related to the use of Sprague-Dawley rats, since inter-individual variability in response to various stressful conditions has been described previously in this rat strain. We therefore compared 3-nitropropionic acid toxicity in rat strains known to be highly (Fisher 344) or poorly (Lewis) responsive to stress and compared the distribution of responses to that of Sprague-Dawley rats. In a protocol of intraperitoneal injection, toxicity of 3-nitropropionic acid was highest in Fisher rats, intermediate in Sprague-Dawley rats and lowest in Lewis rats. In addition, survival curves showed a more heterogeneous response to 3-nitropropionic acid toxicity in Sprague-Dawley rats than that observed in Lewis and Fisher rats. These differences between Sprague-Dawley and Lewis rats were confirmed in a protocol of subcutaneous 3-nitropropionic acid intoxication using osmotic minipumps, where doses up to 36-45mg/kg per day for five days were necessary to induce striatal lesions in Lewis rats as compared to 12-14mg/kg per day for five days in Sprague-Dawley rats. The selectivity of the striatum to lesions, and homogeneous progression of symptoms and neurodegeneration, were more consistently observed in Lewis as compared to Sprague-Dawley rats. These results suggest that vulnerability to 3-nitropropionic acid may depend on genetic factors, which could also influence the physiological response to stress. The present findings also establish an improved model of progressive striatal degeneration in the rat adapted for the testing of new neuroprotective strategies.