Combination of intracortically administered VEGF and environmental enrichment enhances brain protection in developing rats

Postnatal development of the visual cortex is modulated by experience, especially during the critical period. In rats, a stable neuronal population is only acquired after this relatively prolonged period. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor and also has strong neuroprotective, neurotrophic and neurogenic properties. Similar effects have been described for rearing in enriched environments. Our aim is to investigate the vascular and neuronal effects of combining VEGF infusion and environmental enrichment on the visual cortex during the initial days of the critical period. Results showed that a small percentage of Cleaved Caspase-3 positive cells colocalized with neuronal markers. The lesion produced by the cannula implantation resulted in decreased vascular, neuronal and Caspase-3 positive cell densities. Rearing under enriched environment was unable to reverse these effects in any group, whereas VEGF infusion alone partially corrected those effects. A higher effectiveness was reached by combining both the procedures, the most effective combination being when enriched-environment rearing was introduced only after minipump implantation. In addition to the angiogenic effect of VEGF, applied strategies also had synergic neuroprotective effects, and the combination of the two strategies had more remarkable effects than those achieved by each strategy applied individually.     

Physical exercise is required for environmental enrichment to offset the quantitative effects of dark-rearing on the S-100β astrocytic density in the rat visual cortex

After birth, exposure to visual inputs modulates cortical development, inducing numerous changes in all of the components of the visual cortex. Most of the cortical changes thus induced occur during what is called the critical period. Astrocytes play an important role in the development, maintenance and plasticity of the cortex as well as in the structure and function of the vascular network. Visual deprivation induces a decrease in the astroglial population, whereas enhanced experience increases it. Exposure to an enriched environment has been shown to prevent the effects of dark‐rearing in the visual cortex. Our purpose was to study the effects of an enriched environment on the density of astrocytes per reference surface at the visual cortex of dark‐reared rats, in order to determine if enhanced experience is able to compensate the quantitative effects of visual deprivation and the role of physical exercise on the enrichment paradigm. Pregnant Sprague‐Dawley rats were raised in one of the following rearing conditions: control rats with standard housing (12‐h light/dark cycle); in total darkness for the dark‐rearing experiments; and dark‐rearing in conditions of enriched environment without and with physical exercise. The astrocytic density was estimated by immunohistochemistry for S‐100β protein. Quantifications were performed in layer IV. The somatosensorial cortex barrel field was also studied as control. The volume of layer IV was stereologically calculated for each region, age and experimental condition. From the beginning of the critical period, astrocyte density was higher in control rats than in the enriched environment group without physical exercise, with densities of astrocytes around 20% higher at all of the different ages. In contrast, when the animals had access to voluntary exercise, densities were significantly higher than even the control rats. Our main result shows that strategies to apply environmental enrichment should always consider the incorporation of physical exercise, even for sensorial areas such as the visual area, where complex enriched experience by itself is not enough to compensate the effects of visual deprivation.     

Nocturnal high-dose dexamethasone suppression test in the aetiological diagnosis of Cushing's syndrome

Seventeen patients with well-proven Cushing's syndrome (13 with Cushing's disease, 3 with adrenal tumour and 1 presenting ectopic ACTH syndrome caused by bronchial carcinoid) were investigated by using a single-dose 8 mg dexamethasone nocturnal test. The results obtained were compared with those of the classical 8 mg Liddle's test, metyrapone stimulation, plasma ACTH concentration and with the final diagnosis reached through surgery, pathologic anatomy, and/or clinical and biochemical follow-up of the patients after treatment. The diagnostic efficacy or the predictive power of the test (defined as the ratio between the number of cases in which the diagnosis was correctly predicted and the total number of cases), was at least 82.4% vs 84.6% for the classical 8 mg Liddle's test. This percentage increased to 94.1% when the results of repeated tests on three patients with conflicting data were included. It is concluded that the nocturnal high-dose dexamethasone suppression test is a valuable tool in the aetiological diagnosis of Cushing's syndrome.     

Accuracy analysis of complete-arch digital scans in edentulous arches when using an auxiliary geometric device

Statement of problem

Obtaining reliable digital scans of edentulous patients is challenging because of the absence of anatomic landmarks/geometric variations along the dental arch. Whether adding an auxiliary geometric device (AGD) will improve scanning is unclear.

Utilización de transporte sanitario urgente por los pacientes con ictus isquémico e impacto en los tiempos de atención

Introduction

According to numerous studies, using emergency medical services (EMS) to transport stroke patients to hospitals decreases diagnostic and treatment delays.

Morbidity in 303 first‐episode bipolar I disorder patients

Baldessarini RJ, Salvatore P, Khalsa H‐MK, Gebre‐Medhin P, Imaz H, González‐Pinto A, Perez J, Cruz N, Maggini C, Tohen M. Morbidity in 303 first‐episode bipolar I disorder patients.
Bipolar Disord 2010: 12: 264–270. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: To test the hypotheses that: (i) depressive‐dysthymic‐dysphoric (D‐type) morbidity is more prevalent than manic‐hypomanic‐psychotic (M‐type) morbidity even from first episodes of bipolar I disorder (BPD‐I) and despite treatment; (ii) initial presentations predict later morbidity; (iii) morbidity varies internationally; and (iv) early and later morbidity are similar. Methods: We followed SCID‐based, DSM‐IV BPD‐I patients (n = 303) systematically and prospectively for two years to estimate the percent of weeks in specific morbid states from first lifetime major episodes. Results: Total morbidity accounted for 44% of the first two years, and D‐type exceeded M‐type illnesses by 2.1‐fold (30%/14%) among morbidities ranking: mixed states (major + minor) ≥ dysthymia ≥ mania ≥ major depression > hypomania > psychosis. In 164 cases, morbidities at 0.5–2.5 and 2.5–4.5 years were very similar. Depressive or mixed initial episodes predicted a 3.6‐fold excess of D‐type morbidity, and initial M‐type episodes predicted a 7.1‐fold excess of M‐type morbidity over two years. Morbidity in European (EU) sites was nearly half that in the U.S., and 22% greater overall among men than women. In five comparable studies, illness accounted for 54% of follow‐up time, and the ratio of D/M morbidity averaged 3.0. Conclusions: In accord with four midcourse studies, morbidity from BPD‐I onset, despite treatment by community standards, averaged 44%, was 68% D‐type morbidity, and was strongly predicted by first‐episode polarity. Lower morbidity in EU than U.S. sites may reflect differences in healthcare or social systems.     

Effects of visual experience on vascular endothelial growth factor expression during the postnatal development of the rat visual cortex

The development of the cortical vascular network depends on functional maturation. External inputs are an essential requirement in the modeling of the visual cortex, mainly during the critical period, when the functional and structural properties of visual cortical neurons are particularly susceptible to alterations. Vascular endothelial growth factor (VEGF) is the major angiogenic factor, a key signal in the induction of vessel growth. Our study focused on the role of visual stimuli on the development of the vascular pattern correlated with VEGF levels. Vascular density and the expression of VEGF were examined in the primary visual cortex of rats reared under different visual environments (dark rearing, dark-rearing in conditions of enriched environment, enriched environment, and laboratory standard conditions) during postnatal development (before, during, and after the critical period). Our results show a restricted VEGF cellular expression to astroglial cells. Quantitative differences appeared during the critical period: higher vascular density and VEGF protein levels were found in the enriched environment group; both dark-reared groups showed lower vascular density and VEGF levels, which means that enriched environment without the physical exercise component does not exert effects in dark-reared rats.     

Sporadic Creutzfeldt–Jakob disease with glial PrPRes nuclear and perinuclear immunoreactivity

Proteinase K‐resistant prion protein (PrP^Res) nuclear and perinuclear immunoreactivity in oligodendrocytes of the frontal cortex is found in one case of otherwise typical sporadic Creutzfeldt‐Jakob disease (sCJD) type VV2a. The PrP nature of the inclusions is validated with several anti‐PrP antibodies directed to amino acids 130–160 (12F10), 109–112 (3F4), 97–102 (8G8) and the octarepeat region (amino acids 59–89: SAF32). Cellular identification and subcellular localization were evaluated with double‐ and triple‐labeling immunofluorescence and confocal microscopy using antibodies against PrP, glial markers, and histone H3. Based on review of the literature and our own experience, this is a very odd situation that deserves further validation in other cases.     

Lack of experience-mediated differences in the immunohistochemical expression of blood-brain barrier markers (EBA and GluT-1) during the postnatal development of the rat visual cortex

The development of the cortical vascular tree depends on functional development. External inputs are an essential requirement in the modeling of the visual cortex, mainly during the critical period, when congruous blood supply is needed. The blood brain barrier (BBB) function regulates the passage of substances between the blood and the brain parenchyma, which is one of the main differential features of central nervous system (CNS) microvessels. The endothelial barrier antigen (EBA) has been reported as a specific marker for the BBB physiological function in rats. We studied the postnatal development of EBA expression in the visual cortex of rats reared under opposite paradigms of visual experience, e.g., standard laboratory conditions, dark rearing, and enriched environment at 14, 21, 28, 35, 42, 49, 56, and 63 days postnatal (dpn). Parallel sections were immunohistochemically processed for endothelial barrier antigen (EBA) and glucose transporter-1 (GluT-1). Total vasculature was quantified by Lycopersicon esculentum (LEA) lectin histochemistry. No differences in EBA expression were found between groups, although quantitative differences were recorded paralleling differences in vascular density. Paradoxically, there was no expression in certain cortical vessels which were GluT-1 immunopositive and positivity was consistent in non-barrier areas such as the pineal gland. These findings were completely independent of age or experimental conditions. Therefore, the role of the EBA antigen in the BBB remains unclear: it has been undeniably linked to vascular permeability, but its presence in non-barrier vessels suggests another vascular function. Although visual experience modifies vascular density in the visual cortex, it has not been shown to have an influence on the maturation of the BBB function.