Modulation of striatal glutamatergic, dopaminergic and cholinergic neurotransmission pathways concomitant with motor disturbance in rats with kaolin-induced hydrocephalus.

BACKGROUND: Hydrocephalus is characterized by abnormal accumulation of cerebrospinal fluid in the cerebral ventricles and causes motor impairments. The mechanisms underlying the motor changes remain elusive. Enlargement of ventricles compresses the striatum of the basal ganglia, a group of nuclei involved in the subcortical motor circuit. Here, we used a kaolin-injection juvenile rat model to explore the effects of acute and chronic hydrocephalus, 1 and 5 weeks post-treatment, respectively on the three major neurotransmission pathways (glutamatergic, dopaminergic and cholinergic) in the striatum. METHODS: Rats were evaluated for motor impairments. Expressions of presynaptic and postsynaptic protein markers related to the glutamatergic, dopaminergic, and cholinergic connections in the striatum were evaluated. Combined intracellular dye injection and substance P immunohistochemistry were used to distinguish between direct and indirect pathway striatal medium spiny neurons (d and i-MSNs) for the analysis of their dendritic spine density changes. RESULTS: Hydrocephalic rats showed compromised open-field gait behavior. However, male but not female rats displayed stereotypic movements and compromised rotarod performance. Morphologically, the increase in lateral ventricle sizes was greater in the chronic than acute hydrocephalus conditions. Biochemically, hydrocephalic rats had significantly decreased striatal levels of synaptophysin, vesicular glutamate transporter 1, and glutamatergic postsynaptic density protein 95, suggesting a reduction of corticostriatal excitation. The expression of GluR2/3 was also reduced suggesting glutamate receptor compositional changes. The densities of dendritic spines, morphological correlates of excitatory synaptic foci, on both d and i-MSNs were also reduced. Hydrocephalus altered type 1 (DR1) and 2 (DR2) dopamine receptor expressions without affecting tyrosine hydroxylase level. DR1 was decreased in acute and chronic hydrocephalus, while DR2 only started to decrease later during chronic hydrocephalus. Since dopamine excites d-MSNs through DR1 and inhibits i-MSNs via DR2, our findings suggest that hydrocephalus downregulated the direct basal ganglia neural pathway persistently and disinhibited the indirect pathway late during chronic hydrocephalus. Hydrocephalus also persistently reduced the striatal choline acetyltransferase level, suggesting a reduction of cholinergic modulation. CONCLUSIONS: Hydrocephalus altered striatal glutamatergic, dopaminergic, and cholinergic neurotransmission pathways and tipped the balance between the direct and indirect basal ganglia circuits, which could have contributed to the motor impairments in hydrocephalus.

Toxicity, mutagenicity and trace metal constituent of Termitomyces schimperi (Pat.) R. Heim (Lyophyllaceae) and kaolin, a recipe used traditionally in cancer management in Cote d'Ivoire.

ETHNOPHARMACOLOGICAL RELEVANCE: Some local communities in Cote d'Ivoire use the mushroom Termitomyces schimperi combined with kaolin (TSK) to manage various cancers in patients. However, there is a paucity of data on toxicity, mutagenicity and trace metal constituent of TSK. AIM OF THE STUDY: We sought to investigate the acute and sub-chronic toxicities, mutagenic potential, and trace metal constituents of TSK. MATERIALS AND METHODS: To assess acute toxicity, single doses (1000, 3000 and 5000 mg/kg) of aqueous extract of TSK were administrated per os to Sprague Dawley (SD) rats on Day 1. The rats were then monitored for 13 consecutive days. Sub-chronic toxicity was evaluated by daily administration of 200 and 500 mg/kg of the extract per os for 90 consecutive days. SD rats used as control received distilled water. Signs of toxicity, changes in body weight and mortality were monitored. After the aforementioned monitoring processes, rats were sacrificed and blood collected for full blood count and biochemistry analysis. Animal organs were also collected for histopathological examination. The mutagenic potential of the aqueous extract of TSK (10000 µg/mL) on TA98 Salmonella typhimurium was estimated. Additionally, energy-dispersive X-ray fluorescence (ED-XRF) method was employed to determine trace metal constituents of TSK. RESULTS: Single-dose administration of 5000 mg/kg of TSK did not cause any death in the SD rats; thus, LD50 was above 5000 mg/kg. Administration of 1000 and 3000 mg/kg of the aqueous extract of TSK did not cause any significant change in behaviour and body weight of SD rats during the 14-day monitoring period. However, the mean corpuscular volume and the mean corpuscular haemoglobin concentration increased significantly (p < 0.01) among rats administered 1000 and 3000 mg/kg of TSK. There was a significant increase (p < 0.0001) in alanine transaminase levels in rats administered 1000 and 3000 mg/kg of TSK extract compared with control. Conversely, there was a significant decrease (p=0.0122) in serum creatine level among rats administered 1000 and 3000 mg/kg of TSK extract compared with control. After 14 days, there were minimal changes with isolated organs of TSK-treated and control rats. Furthermore, 90-day treatment with extract of TSK caused no significant change in parameters assessed. TSK induced frameshift gene mutation in S. typhimurium before (p < 0.05) and after metabolic activation (p < 0.001). Elemental analysis of TSK revealed the presence of toxic (aluminium) or potentially toxic (silver, rabidium, titanium and zirconium) elements. CONCLUSIONS: The aqueous extract of TSK showed no toxicity (acute and sub-chronic) at doses tested. These findings are consistent with the absence of heavy metals (i.e., cadmium) and potentially toxic elements (i.e., uranium) in TSK samples analysed. TSK showed some level of mutagenic potential. Further mutagenic and chronic toxicity studies on TSK are required.

Respiratory effects induced by occupational exposure to refractory ceramic fibers.

Refractory ceramic fibers (RCFs) are increasingly used as heating-insulated materials in various industries. However, toxicological and epidemiological studies focusing on the adverse effects of RCFs were still insufficient, particularly in China. We conducted a cross-sectional study to evaluate comprehensively the associations between occupational exposure to RCFs and respiratory health effects among Chinese workers. We measured and calculated cumulative RCFexposure levels of RCFs workers from the biggest RCFs factory in China. In total, 430 RCF-exposed workers and 121 controls were enrolled in this study. Physical examinations of the respiratory system were performed and serum levels of biomarkers including Clara cell protein 16 (CC16), surfactant protein D (SP-D), transforming growth factor ß1 (TGF-ß1), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined among all subjects. RCF exposure workers showed a higher prevalence rate of respiratory symptoms (cough: 11.9%) and lower levels of small airways function indices (V50 %: 82.71 ± 20.01, maximal mid expiratory flow (MMEF)%: 81.08 ± 19.56) compared with the control group (cough: 5.0%, V50 %: 90.64 ± 24.36, MMEF%: 88.83 ± 24.22). RCFs workers showed higher levels of TGF-ß1 (31.04 ng/mL) and 8-OHdG (130.72 ng/mL) and lower levels of CC16 (3.68 ng/mL) compared with the controls (TGF-ß1: 26.63 ng/mL, 8-OHdG: 106.86 ng/mL, CC16: 5.65 ng/mL). After adjusting for covariates, cumulative RCF exposure levels showed significant positive associations with the levels of TGF-ß1 and 8-OHdG and negative association with the level of CC16. Occupational RCF exposure could induce adverse respiratory health effects, including cough and small airways damage, which may correlate to the altered levels of lung damage markers (CC16 and TGF-ß1) and oxidative markers (8-OHdG).

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus.

INTRODUCTION: Hydrocephalus is a disorder in which the circulation of cerebrospinal fluid is altered in a manner that leads to its accumulation in the ventricles and subarachnoid space. Its impact on the neuronal density and networks in the overlying cerebral cortex in a time-dependent neonatal hydrocephalic process is largely unknown. We hypothesize that hydrocephalus will affect the cytoarchitecture of the cerebral cortical mantle of neonatal hydrocephalic mice, which will in turn modify sensorimotor processing and neurobehaviour. OBJECTIVE: The purpose of this study is to probe the effect of hydrocephalus on 3 developmental milestones (surface righting reflex, cliff avoidance reflex, and negative geotaxis) and on cortical neuronal densities in neonatal hydrocephalic mice. METHODS: Hydrocephalus was induced in 1-day-old mice by intracisternal injection of sterile kaolin suspension. The pups were tested for reflex development and sensorimotor ability using surface righting reflex (PND 5, 7, and 9), cliff avoidance (PND 6), and negative geotaxis (PND 10 and 12) prior to their sacrifice on PND 7, 14, and 21. Neuronal density and cortical thickness in the sensorimotor cortex were evaluated using atlas-based segmentation of the neocortex and boundary definition in 4-µm paraffin-embedded histological sections with hematoxylin and eosin as well as cresyl violet stains. RESULTS: Surface righting and cliff avoidance activities were significantly impaired in hydrocephalic pups but no statistically significant difference was observed in negative geotaxis in both experimental and control pups. The neuronal density of the sensorimotor cortex was significantly higher in hydrocephalic mice than in age-matched controls on PND 14 and 21 (373.20 ± 21.54 × 10-6 µm2 vs. 157.70 ± 21.88 × 10-6 µm2; 230.0 ± 44.1 × 10-6 µm2 vs. 129.60 ± 3.72 × 10-6 µm2, respectively; p < 0.05). This was accompanied by reduction in the cortical thickness (µm) in the hydrocephalic mice on PND 7 (2,409 ± 43.37 vs. 3,752 ± 65.74, p < 0.05), PND 14 (2,035 ± 322.10 vs. 4,273 ± 67.26, p < 0.05), and PND 21 (1,676 ± 33.90 vs. 4,945 ± 81.79, p < 0.05) compared to controls. CONCLUSION: In this murine model of neonatal hydrocephalus, the quantitative changes in the cortical neuronal population may play a role in the observed changes in neurobehavioural findings.

The Effects of Modified Clay on Abalone (Haliotis discus hannai) Based on Laboratory and Field Experiments.

The abalone industry has suffered immense economic losses due to the occurrence of harmful algal blooms (HABs). Among the methods for mitigating HABs, modified clay is considered the most promising strategy and has been successfully used for field applications in many countries, and its environmental effects have become a subject of global concern. The effects of modified clay on the survival, growth, nutritional quality, and oxidative stress indicators of abalone were studied based on both laboratory and field experiments. The results showed that modified clay at 3-10 times the concentrations used for HAB treatment did not affect the survival of abalone. During the laboratory experiments, the increases in abalone shell length and weight nonsignificantly decreased with increasing concentrations of modified clay at 1-15 d, whereas the weight of abalone in the experimental groups increased rapidly during the recovery period at 16-30 d. The growth and nutrition qualities of abalone in field experiments showed negligible differences between the control and experimental groups. Catalase (CAT) activity in the hepatopancreas and superoxide dismutase (SOD) activity in the gills were significantly affected by certain concentrations of modified clay at individual time points, whereas the malondialdehyde (MDA) content decreased in all experimental groups within 96 h. The removal of bacteria and the mitigation of water quality decline were among the effects of modified clay that contributed to the decrease in MDA content. The present study showed that modified clay had no obvious adverse effects on the survival, growth, quality, or oxidative stress indicators of abalone at the experimental concentrations, thus providing a reference for the field application of modified clay in typical aquaculture areas. Environ Toxicol Chem 2020;39:2065-2075. © 2020 SETAC.

Comparative study of intracisternal kaolin injection techniques to induce congenital hydrocephalus in fetal lamb.

PURPOSE: Kaolin (aluminum silicate) has been used to generate hydrocephalus by direct cisterna magna injection in animal models. The aim of the present study is to compare which method of Kaolin injection into fetal cisterna magna is feasible, safer, and more effective to induce hydrocephalus in fetal lambs. METHODS: Twenty-five well-dated pregnant ewes at gestational 85-90 days (E85-90) were used to compare three different kaolin injection puncture techniques into the fetal cisterna magna. Group 1, ultrasound guidance in a maternal percutaneous transabdominal (TA); group 2, without opening the uterus in a transuterine (TU) technique; group 3, by occipital direct access after exteriorizing fetal head (EFH); and group 4, control group, was normal fetal lambs without injection. The fetal lambs were assessed using lateral ventricle diameter ultrasonographic measurements prior the kaolin injection and on the subsequent days. We analyzed the effectivity, mortality, and fetal losses to determine the best technique to create hydrocephalus in fetal lamb. RESULTS: After fetal intracisternal kaolin (2%, 1mL) injection, lateral ventricle diameters increased progressively in the three different interventional groups compared with the normal values of the control group (p ≤ 0.05). We observed that the transabdominal method had a 60% of fetal losses, considering failure of injection and mortality, compared with the 12.5% in the open group (EFH), and 0% for the transuterine group. CONCLUSIONS: Based on our study, we believe that both, open uterine (EFH) and transuterine approaches are more effective and safer than the transabdominal ultrasound-guided method to induce hydrocephalus.

Light Microscopic Evaluation of Acute and Chronic Hypophyseal Endocrinopathy in a Kaolin-Induced Hydrocephalus Model.

AIM: To demonstrate progression of acute and chronic endocrinopathies in a kaolin-induced hydrocephalus model using light microscopy. MATERIAL AND METHODS: Adult male Sprague-Dawley rats (n = 48) were divided into six groups. Hydrocephalus was induced by intracisternal injection of kaolin solution in the acute and chronic kaolin groups, whereas an identical volume of sterile saline was injected into the sham groups. RESULTS: Somatotropic cell concentrations were lower in the kaolin groups compared with their controls, but there was no difference in somatotropic cell concentration between the acute and chronic kaolin groups. Corticotropic cell concentrations were higher in the acute kaolin and sham groups compared with acute controls. Thyrotropic cell numbers were higher in the acute sham and kaolin groups compared with their controls, and although thyrotropic cell concentations were higher in the acute kaolin group than the acute sham group. No differences were observed between the acute and chronic controls and sham and kaolin groups regarding mammotropicand gonadototropic cell concentations. CONCLUSION: Somatotropic cells are most affected by hydrocephalus that causes pituitary dysfunction, and this effect was more prominent under acute and chronic phases.

Erythropoietin protects the subventricular zone and inhibits reactive astrogliosis in kaolin-induced hydrocephalic rats.

PURPOSE: To elucidate the potential role of erythropoietin (EPO) as a neuroprotective agent against reactive astrogliosis and reducing the thinning rate of subventricular zone (SVZ) in kaolin-induced hydrocephalic rats. METHOD: Thirty-six ten-week-old Sprague-Dawley rats were used in this study. Hydrocephalus was induced with 20% kaolin suspension injected into the cistern of thirty rats and leaving the six rats as normal group. The hydrocephalic rats were randomly divided into hydrocephalic and treatment group. The treatment group received daily dose of recombinant human erythropoietin (rhEPO) from day 7 to day 21 after induction. The animals were sacrificed at 7 (only for hydrocephalic group) and 14 or 21 (for both groups) days after induction. Brain was removed and was prepared for histological analysis by hematoxylin and eosin staining as well as immunohistochemistry for 4-HNE, GFAP, Iba-1, and Ki-67. RESULTS: Histopathological analysis showed that animals treated with rhEPO had a reduced astrocyte reactivity displayed by lower GFAP expression. Hydrocephalic rats received rhEPO also displayed reduced microglial activation shown by lower Iba-1 protein expression. Exogenous rhEPO exerted its protective action in reducing astrogliosis by inhibiting lipid peroxidation that was documented in this study as lower expression of 4-HNE than non-treated group. The SVZ thickness was progressively declining in hydrocephalus group, while the progression rate could be reduced by rhEPO. CONCLUSION: Erythropoietin has a potential use for inhibiting lipid peroxidation, and reactive astrogliosis in hydrocephalic animal model. The reduced thinning rate of SVZ demonstrated that EPO also had effect in reducing the hydrocephalus progressivity. Further research is warranted to explore its efficacy and safety to use in clinical setting.

Parenchymal Pressure Inconsistency in Different Brain Areas After Kaolin Injection into the Subarachnoid Space of Neonatal Rats.

AIM: To describe the relationship between the parenchymal pressure changes and the development of hydrocephalus in kaolininjected neonatal rats according to cerebral regions and time intervals of developing hydrocephalus. MATERIAL AND METHODS: Neonatal rats aged 2 to 3 days were examined in 5 groups as kaolin frontal "K-F", kaolin parietal "KP", saline frontal "SF-F", saline parietal "SF-P" and control "C", based on the injected material and injection sites. All injections were performed into the cortical subarachnoid space of the right frontal and right parietal regions. The fifth group was injection free. On the 3 < sup > rd < /sup > , 7 < sup > th < /sup > , 15 < sup > th < /sup > , 30 < sup > th < /sup > and 60 < sup > th < /sup > days after injection, parenchymal pressures (PP) of 5-7 rats from each group were measured from different regions. RESULTS: We compared the control group with saline-injected and kaolin-injected groups and found statistically significant parenchymal pressure differences based on regional measurements. In the kaolin groups, the mean PP values were obviously higher than the saline-injected group. Within each kaolin-injected group, the pressure values were variable and inconsistent regarding the parenchymal regions. CONCLUSION: Hydrocephalus cannot be totally explained with existent "bulk-flow" or "hydrodynamic" theories. Although our experimental design was planned to develop hydrocephalus according to the bulk flow theory, our results were more compatible with the hydrodynamic theory. The present comments on the occurrence and pathogenesis of hydrocephalus are still open to debate and may require further comprehensive studies.

A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.

AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers. METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes. RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results. CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.

Efficacy and Mode of Action of Kaolin in the Control of Empoasca vitis and Zygina rhamni (Hemiptera: Cicadellidae) in Vineyards.

During 2015, the influence of kaolin applications and bunch-zone leaf removal on the grapevine leafhoppers, Empoasca vitis (Göthe) and Zygina rhamni Ferrari, and their egg parasitoids (Anagrus spp.) was tested in four vineyards of northeastern Italy. The mode of action of kaolin on E. vitis nymphs was also investigated in the laboratory. In the treated plots, kaolin was applied at a rate of 2% w/v on two occasions separated by 5-6 d. In two vineyards, it was applied either on the whole canopy or the bunch zone at the beginning of the E. vitis second generation (preventive criterion), and in the other two vineyards, it was applied to the whole canopy at the peak of the E. vitis third generation (curative criterion). Both the preventive and curative kaolin applications caused a significant decrease in the populations of E. vitis and Z. rhamni nymphs. The effect of the preventive applications was persistent and was associated with reduced E. vitis leaf symptoms. Kaolin did not influence the activity of Anagrus spp. Bunch-zone leaf removal did not affect leafhopper populations. Laboratory experiments showed that inhibition of feeding was the main mode of action through which kaolin affected nymph populations. Based on these outcomes, kaolin could be a valuable alternative to synthetic insecticides in controlling grapevine leafhoppers.

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

PURPOSE: We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. METHODS: Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. RESULTS: The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. CONCLUSIONS: We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus.

Differential contributions of vasopressin V1A and oxytocin receptors in the amygdala to pain-related behaviors in rats.

Neuroplastic changes in the amygdala account for emotional-affective aspects of pain and involve neuropeptides such as calcitonin gene-related peptide and corticotropin-releasing factor. Another neuropeptide system, central arginine vasopressin, has been implicated in neuropsychiatric disorders, but its role in pain-related emotional expression and neuroplasticity remains to be determined. Here, we tested the hypothesis that arginine vasopressin in the amygdala contributes to pain-related emotional-affective responses, using stereotaxic applications of arginine vasopressin and antagonists for G-protein coupled vasopressin V1A and oxytocin receptors in adult male Sprague-Dawley rats. In normal animals, arginine vasopressin increased audible and ultrasonic vocalizations and anxiety-like behavior (decreased open-arm preference in the elevated plus maze). The facilitatory effects were blocked by a selective V1A antagonist (SR 49059, Relcovaptan) but not by an oxytocin receptor antagonist (L-371,257). L-371,257 had some facilitatory effects on vocalizations. Arginine vasopressin had no effect in arthritic rats (kaolin/carrageenan knee joint pain model). SR 49059 inhibited vocalizations and anxiety-like behavior (elevated plus maze) in arthritic, but not normal, rats and conveyed anxiolytic properties to arginine vasopressin. Arginine vasopressin, SR 49059, and L-371,257 had no significant effects on spinal reflexes. We interpret the data to suggest that arginine vasopressin through V1A in the amygdala contributes to emotional-affective aspects of pain (arthritis model), whereas oxytocin receptors may mediate some inhibitory effects of the vasopressin system.

A Novel Experimental Animal Model of Adult Chronic Hydrocephalus.

BACKGROUND: The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown. OBJECTIVE: To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus. METHODS: Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed. RESULTS: Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement. CONCLUSION: Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus. ABBREVIATION: NPH, normal pressure hydrocephalus.

Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy.

Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note.

BACKGROUND: Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools. OBJECTIVE: The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats. METHODS: We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion. RESULTS: Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals. CONCLUSIONS: An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.

Effects of Kaolin on Lobesia botrana (Lepidoptera: Tortricidae) and Its Compatibility With the Natural Enemy, Trichogramma cacoeciae (Hymenoptera: Trichogrammatidae).

Lobesia botrana (Denis and Schiffermüller) (Lepidoptera: Tortricidae) is an important grapevine pest in Europe recently encountered in America. Trichogramma cacoeciae Marchal (Hymenoptera: Trichogrammatidae) is amongst the most effective parasitoids for Lepidopteran species. Studies to evaluate the effect of kaolin, an inert, nontoxic mineral, on oviposition, egg hatch, and neonate mortality of these species were carried out. Efficacy on L. botrana neonate larvae, oviposition, and egg hatch was evaluated. Effects of kaolin on parasitism and emergence of T. cacoeciae from L. botrana and Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae) eggs were also evaluated. Lobesia botrana egg hatch and oviposition rates were reduced, and neonate larvae mortality was significantly greater in kaolin-treated arenas and when included in synthetic neonate larvae diet. Kaolin had no effect on T. cacoeciae parasitism in both hosts. There was only a slight but statistically insignificant effect on T. cacoeciae progeny emergence from L. botrana eggs and no effect from E. kuehniella. The results involving reductions in L. botrana oviposition and egg hatch and increase in larval mortality with kaolin suggest this compound may contribute to reduction in population densities and can be considered in rational integrated pest management strategies for L. botrana. Due to the laboratory results presented on parasitoid emergence, even though field bioassays would give a more exhaustive evaluation, it appears kaolin can be compatible with T. cacoeciae in L. botrana management.

CSF flow pathways through the ventricle-cistern interfaces in kaolin-induced hydrocephalus rats-laboratory investigation.

PURPOSE: The goal of this study was to identify direct cerebrospinal fluid (CSF) pathways in the interface between ventricles and cisterns. Such routes are hypothesized to be involved in alternative CSF flows in abnormal circumstances of CSF circulation. METHODS: Chronic obstructive hydrocephalus models were induced in ten Sprague-Dawley rats with kaolin injection into the cisterna magna. Three weeks after the kaolin injection, when thick arachnoid fibrosis obliterated the fourth ventricular outlets, cationized ferritin was stereotactically infused as a tracer into the lateral ventricle in order to observe the pathways from the ventricles to the subarachnoid space. Animals were killed in 48 h and brains were sectioned. CSF flow pathways were traced by the staining of ferritin with ferrocyanide. RESULTS: Eight out of ten rats developed hydrocephalus. The subarachnoid membranes of the convexity and basal cisterns were severely adhered such that most of the ferritin remained in the ventricles whereas basal and convexity cisterns were clear of ferritin. In six out of the eight hydrocephalus rats, ferritin leaked from the third ventricle into the quadrigeminal cistern, and from the lateral ventricle into the ambient cistern. CONCLUSIONS: The interfaces between the third ventricle and the quadrigeminal cistern, and between the lateral ventricle and the ambient cistern appear to be alternative CSF pathways in a pathologic condition such as obstructive hydrocephalus.