The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia?

Hypertension is a main risk factor for cerebrovascular disease, including vascular dementia. The present study was designed to evaluate if hypertension-dependent changes of the hippocampus of spontaneously hypertensive rats (SHR) of different ages were related with those occurring in vascular dementia. The hippocampus was chosen as the brain area involved in learning and memory. Systolic pressure was slightly increased in 2-month-old SHR in comparison with age-matched normotensive Wistar-Kyoto (WKY) rats and augmented progressively with age in SHR. No microanatomical changes were observed in the hippocampus of SHR of 2 months in comparison with age-matched WKY rats. A limited decrease of white matter volume was observed in 4-month-old SHR. In SHR of 6 months, a reduction of grey matter volume both in the CA1 subfield and in the dentate gyrus occurred. Evaluation of phosphorylated 200-kDa neurofilament immunoreactivity revealed a decreased immune reaction area in the CA1 subfield of 6-month-old SHR compared to age-matched WKY rats and no changes in the expression and localization of the dendritic marker microtubule associated protein (MAP)-2. In 6-month-old SHR, an increase of glial fibrillary acidic protein (GFAP)-expression was found by Western blot analysis. Immunohistochemistry revealed an increase in number (hyperplasia), but not in size of astrocytes. These findings indicate the occurrence of cytoskeletal breakdown and astroglial changes primarily in the CA1 subfield of the hippocampus of SHR of 6 months. The occurrence in the hippocampus of SHR of regressive changes and astroglial reaction similar to those occurring in neurodegenerative disorders with cognitive impairment suggests that they represent an animal model of vascular dementia.     

Neonatal exposure to chlorpyrifos affects maternal responses and maternal aggression of female mice in adulthood

CD-1 mice were exposed to the organophosphate pesticide chlorpyrifos (CPF) throughout postnatal days (PND) 11–14 at the subtoxic dose of 3 mg/kg. At adolescent age, females and males underwent a sociability test in which level of sociability and social preference were measured. At adulthood only females' behavior was analyzed. Maternal behavior of CPF-exposed females was assessed on postpartum day 1 after removal of the pups for 1 h, while anxiety levels were measured in a 5 min dark–light test on postpartum day 2. Nest defense response to an unfamiliar male intruder was assessed on postpartum day 7. In addition, from birth to postpartum day 7 a detailed analysis of nest building activity was carried out. Neonatal CPF exposure does not interfere with social behavior and social preferences at adolescence, whereas at adulthood it induces significant behavioral alterations in lactating females. Motivation to build and defend the nest was decreased in CPF females that were also less anxious than controls in the dark–light paradigm. These results confirm that developmental exposure to CPF induces long-lasting alterations in selected sexual-dimorphic responses of the adult social repertoire, and suggest that early exposure to CPF might interfere with hypothalamic neuroendocrine mechanisms regulating social responses.     

The apolipoprotein E ɛ4 allele and memory performance in HIV-1 seropositive subjects: differences at baseline but not after acute oral lorazepam challenge

Rationale  The APOE ɛ4 allele, an established genetic risk factor for late-onset Alzheimer’s disease, has been linked to an increased risk for dementia especially in older individuals with HIV-1 infection. This allele has also been associated with increased memory impairment following oral lorazepam challenge in healthy elderly. Lorazepam and other benzodiazepines are widely prescribed in individuals with HIV-1 infection who are at increased risk for cognitive impairment. Objective  The aim of this study was to examine if the ɛ4 allele influences lorazepam-induced memory deficits in this population. Materials and methods  Forty-one non-demented, HIV-1 seropositive adults (15 ɛ4 carriers, mean age = 43.47 ± 8.25; 26 ɛ4 non-carriers, mean age = 46.77 ± 8.56) participated in a double-blind, placebo-controlled crossover design, receiving single acute oral doses of lorazepam 0.5, 1.0 mg, or placebo over three sessions, each 1 week apart. Standardized neuropsychological assessments, including measures of immediate and delayed verbal recall, were conducted at baseline and at 1, 2.5, and 5 h post-drug administration in each condition. Results  Acute lorazepam administration produced dose- and time-dependent impairments in measures of verbal recall. However, the e4 allele did not modulate these adverse effects. An APOE ɛ4 group by time interaction was also found such that the APOE-ɛ4-positive subjects had significantly better immediate and delayed verbal recall than the negative subjects at baseline assessment, but the groups did not significantly differ at any subsequent time point. Conclusion  Future studies should clarify the role of ɛ4 in the modulation of drug-induced cognitive toxicity and baseline performance and their relationship to progressive decline, especially in older individuals with HIV-1 infection, a group at increased risk for dementia. All analyses were repeated (not reported here, available upon request) in the subgroup of individuals currently meeting CDC surveillance case definition for AIDS (Center for Disease Control and Prevention 1992; n = 30; 12 ɛ4+/18 ɛ4−). The pattern of findings was replicated.     

Cognitive performance of healthy young rats following chronic donepezil administration

Rationale Experimental studies have investigated the effects of chronic donepezil treatment on the behavioral deficits elicited by reduced activity or the loss of cholinergic neurons that occurs in aging or in models of dementia. However, few studies have analyzed the effects of chronic donepezil treatment on the cognitive functions of intact animals. Objectives The cognitive functions of healthy young rats treated chronically with the acetylcholinesterase inhibitor donepezil were evaluated using a wide behavioral test battery. Results Chronic treatment with donepezil ameliorated memory functions and explorative strategies, speeded up the acquisition of localizing knowledge, augmented responsiveness to the context, and reduced anxiety levels. However, it did not affect spatial span, modify motivational levels, or influence associative learning. Conclusions The present findings show the specific profile of donepezil action on cognitive functions in the presence of unaltered cholinergic neurotransmission systems.     

Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps

Objectives

To explore the role of diffusion tensor imaging (DTI)-based histogram analysis and functional diffusion maps (fDMs) in evaluating structural changes of low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy.

Methods

Twenty-one LGG patients underwent 3T-MR examinations before and after three and six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery (FLAIR) sequences and DTI (b?=?1000 s/mm², 32 directions). Mean diffusivity (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q) were obtained. Histogram and fDM analyses were performed on co-registered baseline and post-chemotherapy maps. DTI changes were compared with modifications of tumour area and volume [according to Response Assessment in Neuro-Oncology (RANO) criteria], and seizure response.

Results

After three cycles of TMZ, 20/21 patients were stable according to RANO criteria, but DTI changes were observed in all patients (Wilcoxon test, P?≤?0.03). After six cycles, DTI changes were more pronounced (P?≤?0.005). Seventy-five percent of patients had early seizure response with significant improvement of DTI values, maintaining stability on FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume change (R²?=?0.614 and 0.561, P?<?0.0005, respectively). TMZ-related changes were located mainly at tumour borders on p and MD fDMs.

Conclusions

DTI-based histogram and fDM analyses are useful techniques to evaluate the early effects of TMZ chemotherapy in LGG patients.

Key Points

? DTI helps to assess the efficacy of chemotherapy in low-grade gliomas. ? Histogram analysis of DTI metrics quantifies structural changes in tumour tissue. ? Functional diffusion maps (fDMs) spatially localize the changes of DTI metrics. ? Changes in DTI histograms and fDMs precede changes in conventional MRI. ? Early changes in DTI histograms and fDMs correlate with seizure response.

     

Synthesis and activity of phenyl derivatives containing 5,6-dimethylthieno[2,3-d]pyrimidin-4(1H)-one or 4H-pyrimido[5,4-b]indol-4-one heterocyclic system as potential nonsteroidal anti-inflammatory drugs

The synthesis, the analgesic and anti-inflammatory activities of two series of phenyl derivatives containing 5,6-dimethyl-thieno[2,3-d]pyrimidin-4(1H)-one and 4H-pyrimido[5,4-b]indol-4-one system, respectively, are reported. Two of these derivatives, 6A and 9B, showed interesting activities. The results of the pharmacological assays are discussed.     

Catalytic Abatement of Volatile Organic Compounds and Soot over Manganese Oxide Catalysts

A set of manganese oxide catalysts was synthesized via two preparation techniques: solution combustion synthesis (Mn₃O₄/Mn₂O₃-SCS and Mn₂O₃-SCS) and sol-gel synthesis (Mn₂O₃-SG550 and Mn₂O₃-SG650). The physicochemical properties of the catalysts were studied by means of N₂-physisorption at −196 °C, X-ray powder diffraction, H₂ temperature-programmed reduction (H₂-TPR), soot-TPR, X-ray photoelectron spectroscopy (XPS) and field-emission scanning electron microscopy (FESEM). The high catalytic performance of the catalysts was verified in the oxidation of Volatile Organic Compounds (VOC) probe molecules (ethene and propene) and carbon soot in a temperature-programmed oxidation setup. The best catalytic performances in soot abatement were observed for the Mn₂O₃-SG550 and the Mn₃O₄/Mn₂O₃-SCS catalysts. The catalytic activity in VOC total oxidation was effectively correlated to the enhanced low-temperature reducibility of the catalysts and the abundant surface O_α-species. Likewise, low-temperature oxidation of soot in tight contact occurred over the Mn₂O₃-SG550 catalyst and was attributed to high amounts of surface O_α-species and better surface reducibility. For the soot oxidation in loose contact, the improved catalytic performance of the Mn₃O₄/Mn₂O₃-SCS catalyst was attributed to the beneficial effects of both the morphological structure that—like a filter—enhanced the capture of soot particles and to a probable high amount of surface acid-sites, which is characteristic of Mn₃O₄ catalysts.