Inhibition of VEGFR-2 by SU5416 increases neonatally glutamate-induced neuronal damage in the cerebral motor cortex and hippocampus.

Vascular endothelial growth factor (VEGF) exerts neuroprotective or proinflammatory effects, depending on what VEGF forms (A-E), receptor types (VEGFR1-3), and intracellular signaling pathways are involved. Neonatal monosodium glutamate (MSG) treatment triggers neuronal death by excitotoxicity, which is commonly involved in different neurological disorders, including neurodegenerative diseases. This study was designed to evaluate the effects of VEGFR-2 inhibition on neuronal damage triggered by excitotoxicity in the cerebral motor cortex (CMC) and hippocampus (Hp) after neonatal MSG treatment. MSG was administered at a dose of 4 g/kg of body weight (b.w.) subcutaneously on postnatal days (PD) 1, 3, 5, and 7, whereas the VEGFR-2 inhibitor SU5416 was administered at a dose of 10 mg/kg b.w. subcutaneously on PD 5 and 7, 30 min before the MSG treatment. Neuronal damage was assessed using hematoxylin and eosin staining, fluoro-Jade staining, and TUNEL assay. Additionally, western blot assays for some proteins of the VEGF-A/VEGFR-2 signaling pathway (VEGF-A, VEGFR-2, PI3K, Akt, and iNOS) were carried out. All assays were performed on PD 6, 8, 10, and 14. Inhibition of VEGFR-2 signaling by SU5416 increases the neuronal damage induced by neonatal MSG treatment in both the CMC and Hp. Moreover, neonatal MSG treatment increased the expression levels of the studied VEGF-A/VEGFR-2 signaling pathway proteins, particularly in the CMC. We conclude that VEGF-A/VEGFR-2 signaling pathway activation could be part of the neuroprotective mechanisms that attempt to compensate for neuronal damage induced by neonatal MSG treatment and possibly also in other conditions involving excitotoxicity.

Short-term administration of tibolone reduces inflammation and oxidative stress in the hippocampus of ovariectomized rats fed high-fat and high-fructose.

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

Down Regulation of Catsper1 Expression by Calmodulin Inhibitor (Calmidazolium): Possible Implications for Fertility.

The CatSper channel localizes exclusively in the flagella of sperm cells. The Catsper1 protein, together with three pore units, is essential for the CatSper Channel formation, which produces flagellum hyperactivation and confers sperm fertility. Catsper1 expression is dependent on Sox transcription factors, which can recognize in vitro at least three Sox binding sites on the promoter. Sox transcription factors have calmodulin-binding domains for nuclear importation. Calmodulin (CaM) is affected by the specific inhibitor calmidazolium (CMZ), which prevents the nuclear transport of Sox factors. In this work, we assess the regulation of the Catsper1 promoter in vivo by Sox factors in the murine testis and evaluate the effects of the inhibitor calmidazolium on the expression of the Casper genes, and the motility and fertility of the sperm. Catsper1 promoter has significant transcriptional activity in vivo; on the contrary, three Sox site mutants in the Catsper1 promoter reduced transcriptional activity in the testis. CaM inhibition affects Sox factor nuclear transport and has notable implications in the expression and production of Catsper1, as well as in the motility and fertility capability of sperm. The molecular mechanism described here might conform to the basis of a male contraceptive strategy acting at the transcriptional level by affecting the production of the CatSper channel, a fundamental piece of male fertility.

Investigation of Different Winemaking Protocols to Mitigate Smoke Taint Character in Wine.

There is an increase in the levels of volatile phenols in wine made with smoke-impacted grapes. These compounds are present in wood smoke resulting from the pyrolysis (thermal decomposition) of lignin and at high levels give overpowering smoky and ashy characters to a wine. This research aimed to compare all the suggested wine mitigation strategies that evolved from prior research using smoke-impacted grapes under identical winemaking conditions except for the parameter under investigation. Cabernet Sauvignon grapes were received from three areas with varying amounts of smoke exposure in Northern California. Gas chromatography combined with mass spectrometry (GC-MS) and descriptive analyses were performed to correlate the volatile phenol composition to smoke taint characteristics. The winemaking variables investigated were the use of different fermentation yeasts, oak additions, and fermentation temperatures. Among other attributes, smokiness and ashy aftertaste were significantly different among the wines, showing a clear difference between the wines made from smoke-impacted fruit and the control wines made from non-impacted fruit. Findings indicate that mitigation strategies during red wine fermentation have a limited impact on the extraction of smoke-taint markers and the expression of smoke-taint sensory characteristics.

Noninvasive transcranial focal stimulation affects the convulsive seizure-induced P-glycoprotein expression and function in rats.

Transcranial focal stimulation (TFS) is a noninvasive neuromodulation strategy that reduces seizure activity in different experimental models. Nevertheless, there is no information about the effects of TFS in the drug-resistant phenotype associated with P-glycoprotein (Pgp) overexpression. The present study focused on determining the effects of TFS on Pgp expression after an acute seizure induced by 3-mercaptopropionic acid (MPA). P-glycoprotein expression was analyzed by western blot in the cerebral cortex and hippocampus of rats receiving 5 min of TFS (300 Hz, 50 mA, 200 µs, biphasic charge-balanced squared pulses) using a tripolar concentric ring electrode (TCRE) prior to administration of a single dose of MPA. An acute administration of MPA induced Pgp overexpression in cortex (68 ±â€¯13.4%, p < 0.05 vs the control group) and hippocampus (48.5 ±â€¯14%, p < 0.05, vs the control group). This effect was avoided when TFS was applied prior to MPA. We also investigated if TFS augments the effects of phenytoin in an experimental model of drug-resistant seizures induced by repetitive MPA administration. Animals with MPA-induced drug-resistant seizures received TFS alone or associated with phenytoin (75 mg/kg, i.p.). TFS alone did not modify the expression of the drug-resistant seizures. However, TFS combined with phenytoin reduced seizure intensity, an effect associated with a lower prevalence of major seizures (50%, p = 0.03 vs phenytoin alone). Our experiments demonstrated that TFS avoids the Pgp overexpression induced after an acute convulsive seizure. In addition, TFS augments the phenytoin effects in an experimental model of drug-resistant seizures. According with these results, it is indicated that TFS may represent a new neuromodulatory strategy to revert the drug-resistant phenotype.

Expression of VEGF- and tight junction-related proteins in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy.

The blood-brain barrier (BBB) maintains the optimal microenvironment for brain function. Tight junctions (TJs) allow endothelial cells to adhere to each other, leading to the formation of a barrier that prevents the penetration of most molecules via transcellular routes. Evidence has indicated that seizure-induced vascular endothelial growth factor (VEGF) type 2 receptor (VEGFR-2) pathway activation weakens TJs, inducing vasodilatation and increasing vascular permeability and subsequent brain injury. The present study focused on investigating the expression levels of VEGF-related (VEGF-A and VEGFR-2) and TJ-related proteins (claudin-5, occludin and ZO-1) in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy (TLE). The results obtained from hippocampal sclerosis TLE (HS-TLE) patients were compared with those obtained from patients with TLE secondary to lesions (lesion-TLE) and autopsy samples. The Western blotting and immunofluorescence results showed that VEGF-A and VEGFR-2 protein expression levels were increased in HS-TLE and lesion-TLE patients compared to autopsy group. On the other hand, claudin-5 expression was higher in HS-TLE patients and lesion-TLE patients than autopsies. The expression level of occludin and ZO-1 was decreased in HS-TLE patients. Our study described modifications to the integrity of the BBB that may contribute to the pathogenesis of TLE, in which the VEGF system may play an important role. We demonstrated that the same modifications were present in both HS-TLE and lesion-TLE patients, which suggests that seizures modify these systems and that they are not associated with the establishment of epilepsy.

Repeated ketamine administration induces recognition memory impairment together with morphological changes in neurons from ventromedial prefrontal cortex, dorsal striatum, and hippocampus.

Ketamine is an anesthetic agent that antagonizes N-methyl-d-aspartate receptors, inducing psychotic-like symptoms in healthy humans and animals. This agent has been used as a pharmacological tool for studying biochemical and physiological mechanisms underlying the clinical manifestations of schizophrenia. The main goal of this study was to evaluate the effect of repeated injections of ketamine (5 and 10 mg/kg, i.p., daily for 5 days) on recognition memory and neuronal morphology in ICR-CD1 mice. This treatment induced recognition memory impairment in the novel object recognition test and a decrease in dendritic spines density in both dorsal striatum and CA1-hippocampus. Sholl analysis showed that both ketamine doses decrease the dendritic arborization in ventromedial prefrontal cortex, dorsal striatum, and CA1-hippocampus. Finally, dendritic spines morphology was modified by both doses; that is, an increase of the filipodia-type spines (10 mg/kg) and a reduction of the mushroom-type spines (5 and 10 mg/kg) was observed in the ventromedial prefrontal cortex. In the dorsal striatum, the low dose of ketamine induced an increase in long thin spines and a decrease of mushroom spines. Interestingly, in CA1-hippocampus, there was an increase in the mushrooms type spines (5 mg/kg). Current findings suggest that the subchronic blockade of N-methyl-d-aspartate receptor changes the neuronal plasticity of several brain regions putatively related to recognition memory impairment.

Recovery of motor function after traumatic spinal cord injury by using plasma-synthesized polypyrrole/iodine application in combination with a mixed rehabilitation scheme.

Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased ßIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as ßIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and ßIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of ßIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.

Application of Classification Algorithms to Diffuse Reflectance Spectroscopy Measurements for Ex Vivo Characterization of Biological Tissues.

Biological tissue identification in real clinical scenarios is a relevant and unsolved medical problem, particularly in the operating room. Although it could be thought that healthy tissue identification is an immediate task, in practice there are several clinical situations that greatly impede this process. For instance, it could be challenging in open surgery in complex areas, such as the neck, where different structures are quite close together, with bleeding and other artifacts affecting visual inspection. Solving this issue requires, on one hand, a high contrast noninvasive technique and, on the other hand, powerful classification algorithms. Regarding the technique, optical diffuse reflectance spectroscopy has demonstrated such capabilities in the discrimination of tumoral and healthy biological tissues. The complex signals obtained, in the form of spectra, need to be adequately computed in order to extract relevant information for discrimination. As usual, accurate discrimination relies on massive measurements, some of which serve as training sets for the classification algorithms. In this work, diffuse reflectance spectroscopy is proposed, implemented, and tested as a potential technique for healthy tissue discrimination. A specific setup is built and spectral measurements on several ex vivo porcine tissues are obtained. The massive data obtained are then analyzed for classification purposes. First of all, considerations about normalization, detrending and noise are taken into account. Dimensionality reduction and tendencies extraction are also considered. Featured spectral characteristics, principal component or linear discrimination analysis are applied, as long as classification approaches based on k-nearest neighbors (k-NN), quadratic discrimination analysis (QDA) or Naïve Bayes (NB). Relevant parameters about classification accuracy are obtained and compared, including ANOVA tests. The results show promising values of specificity and sensitivity of the technique for some classification algorithms, even over 95%, which could be relevant for clinical applications in the operating room.

REST/NRSF transcription factor is overexpressed in hippocampus of patients with drug-resistant mesial temporal lobe epilepsy.

The Repressor Element-1 Silencing Transcription factor or Neuron-Restrictive Silencer Factor (REST/NRSF) is a zinc finger repressor transcription factor of the Kruppel family. Several studies in experimental models have shown that overexpression of REST/NRSF occurs after the induction of seizures. In the present study, the expression of REST/NRSF (messenger ribonucleic acid (mRNA) and protein) was evaluated in the hippocampus of 28 patients with drug-resistant mesial temporal lobe epilepsy (MTLE) and their correlation with clinical variables and comorbid anxiety and depression. The REST/NRSF protein expression was augmented in an age-dependent manner in the hippocampus of autopsied subjects. However, this condition was not observed in patients with MTLE, in whom overexpression of this transcription factor occurred at both the mRNA and protein levels. The correlations with clinical variables showed that the frequency of epileptic seizures was proportional to the protein expression of REST/NRSF. The results revealed that the overexpression of REST/NRSF was more evident in patients with MTLE without anxiety and depression. Our data indicate that the expression of REST/NRSF is modified in patients with MTLE. This condition has implications in the pathophysiology of this disorder, making it a potential candidate for the optimization of clinical treatments.

Evaluación semicuantitativa de gliomas cerebrales en adultos: un enfoque de las características neuropatológicas.

INTRODUCTION: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. OBJECTIVE: To develop a semi-quantitative scale to numerically grade gliomas morphological characteristics. METHOD: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. RESULTS: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). CONCLUSIONS: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.

INTRODUCCIÓN: Los gliomas son neoplasias con alta recurrencia y mortalidad. Por la dificultad para aplicar la clasificación de la Organización Mundial de la Salud (2016), los países en desarrollo siguen utilizando la evaluación histológica para diagnosticarlos y clasificarlos. OBJETIVO: Desarrollar una escala semicuantitativa para calificar numéricamente las características morfológicas de los gliomas. MÉTODO: Cohorte de pacientes con gliomas evaluada y seguida durante 36 meses. Se analizaron y calificaron cortes del tejido tumoral, incluyendo aspectos como estirpe celular, celularidad, pleomorfismo nuclear, mitosis, hiperplasia endotelial, cambios hipóxicos, cuerpos apoptóticos, necrosis, hemorragia e índice de proliferación. RESULTADOS: Se analizaron 58 casos. La mediana de la calificación de los gliomas de bajo grado fue de 12 puntos (percentiles 25 y 75 de 9 y 13.5, respectivamente) y la de los gliomas de alto grado fue de 17 puntos (percentiles 25 y 75 de 16 y 20.5, ­respectivamente) (p < 0.0001). La supervivencia a 36 meses de los pacientes con gliomas de bajo (13/17) y alto grado (6/41) también fue significativamente diferente (p < 0.0001). CONCLUSIONES: La escala morfológica semicuantitativa permite una evaluación objetiva de los gliomas, con una adecuada correlación entre la calificación, el grado del tumor y el tiempo de supervivencia.

Semi-quantitative evaluation of brain gliomas in adults: A focus on neuropathological characteristics.

INTRODUCTION: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. OBJECTIVE: To develop a semi-quantitative scale to numerically grade gliomas by its morphological characteristics. METHOD: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. RESULTS: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). CONCLUSIONS: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.

Sodium cromoglycate reduces short- and long-term consequences of status epilepticus in rats.

Several studies indicate that sodium cromoglycate (CG) induces neuroprotective effects in acute neurological conditions. The present study focused on investigating if the use of CG in rats during the post-status epilepticus (post-SE) period reduces the acute and long-term consequences of seizure activity. Our results revealed that animals that received a single dose of CG (50 mg/kg s.c.: subcutaneously) during the post-SE period showed a lower number of neurons in the process of dying in the dentate gyrus, hilus, cornu ammonis 1 (CA1), and CA3 of the dorsal hippocampus than the rats that received the vehicle. However, this effect was not evident in layers V-VI of the sensorimotor cortex or the lateral-posterior thalamic nucleus. A second experiment showed that animals that received CG subchronically (50 mg/kg s.c. every 12 h for 5 days followed by 24 mg/kg/day s.c. for 14 days using osmotic minipumps) after SE presented fewer generalized convulsive seizures and less neuronal damage in the lateral-posterior thalamic nucleus but not in the hippocampus or cortex. Our data indicate that CG can be used as a therapeutic strategy to reduce short- and long-term neuronal damage in the hippocampus and thalamus, respectively. The data also indicate that CG can reduce the expression of generalized convulsive spontaneous seizures when it is given during the latent period of epileptogenesis.

High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1.

Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive, and have limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Although it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was recently identified in ocular tissues. In this article we examined the involvement of the GAPDH/Siah1 interaction in human retinal pericyte (hRP) apoptosis. HRP were cultured in 5 mm normal glucose, 25 mm l- or d-glucose for 48 h (osmotic control and high glucose treatments, respectively). Siah1 siRNA was used to down-regulate Siah1 expression. TAT-FLAG GAPDH and/or Siah1-directed peptides were used to block GAPDH and Siah1 interaction. Co-immunoprecipitation assays were conducted to analyze the effect of high glucose on the association of GAPDH and Siah1. Apoptosis was measured by Annexin V staining and caspase-3 enzymatic activity assay. High glucose increased Siah1 total protein levels, induced the association between GAPDH and Siah1, and led to GAPDH nuclear translocation. Our findings demonstrate that dissociation of the GAPDH/Siah1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of DR. Thus, the work presented in this article can provide a foundation to identify novel targets for early treatment of DR.

Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a condition producing irreversible damage to the neurological function. Among the leading mechanisms associated to cell death after SCI, excitotoxicity, oxidative stress, inflammatory response and apoptosis are considered potential targets to prevent tissue damage. We recently reported that dapsone an anti-inflammatory drug, decreases the activity of myeloperoxidase, lipid peroxidation, improve neurological function and increase the amount of spared tissue after SCI in rats. In this study, we characterized the anti-apoptotic effect of dapsone administered at 12.5 mg/kg/24 h dose, starting at 3 and 5 h after SCI. We monitored the activity of caspases-8, 9, and 3 and quantitated Annexin V and TUNEL positive cells in the core of the lesion. Results showed increased activities of caspase-8, 9 and 3 at 72 h by SCI to reach increments of 69, 143 and 293 %, respectively, as compared to sham group. Meanwhile, dapsone, administered at 3 and 5 after SCI, reduced caspase-8 activity by 36 and 44 % respectively, whereas the activity of caspase-9 was diminished by 37 %. Likewise, the activity of caspase-3 showed a decrease of 38 %. Finally, both Annexin V and TUNEL-positive cells were significantly reduced by DDS as compared to untreated SCI animals. Results showed that dapsone exerted anti-apoptotic effect after SCI.

The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection.

Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model.

Do certain signal transduction mechanisms explain the comorbidity of epilepsy and mood disorders?

It is well known that mood disorders are highly prevalent in patients with epilepsy. Although several studies have aimed to characterize alterations in different types of receptors associated with both disturbances, there is a lack of studies focused on identifying the causes of this comorbidity. Here, we described some changes at the biochemical level involving serotonin, dopamine, and γ-aminobutyric acid (GABA) receptors as well as signal transduction mechanisms that may explain the coexistence of both epilepsy and mood disorders. Finally, the identification of common pathophysiological mechanisms associated with receptor-receptor interaction (heterodimers) could allow designing new strategies for treatment of patients with epilepsy and comorbid mood disorders.

Adult norms for the decision-making MindPulse Digital Test.

We present adult normalized data for MindPulse (MP), a new tool evaluating attentional and executive functioning (AEF) in decision-making. We recruited 722 neurotypical participants (18-80 years), with 149 retested. The MP test includes three tasks: Simple Reaction Time (SRT), Go/No-go, and complex Go/No-go, involving perceptual components, motor responses, and measurements of reaction time (RT) and correctness. We compare responses, evaluating 14 cognitive indices (including new composite indices to describe AEF: Executive Speed and Reaction to Difficulty). We adjust for age/sex effects, introduce a difficulty scale, and consider standard deviations, aberrant times, and Spearman Correlation for speed-accuracy balance. Wilcoxon unpaired rank test is used to assess sex effects, and linear regression is employed to assess the age linear dependency model on the normalized database. The study demonstrated age and sex effects on RTs, in all three subtests, and the ability to correct it for individual results. The test showed excellent validity (Cronbach Alpha for the three subtasks is 92, 87, 95%) and high internal consistency (p < 0.001 for each subtask significantly faster than the more complex subtask) of the MP across the wide age range. Results showed correlation within the three RT parts of the test (p < .001 for each) and the independence of SRT, RD, and ES indices. The Retest effect was lower than intersubject variance, showing consistency over time. This study highlights the MP test's strong validity on a homogeneous, large adult sample. It emphasizes assessing AEF and Reaction to Difficulty dynamically with high sensitivity.

Effects of transcranial focal electrical stimulation alone and associated with a sub-effective dose of diazepam on pilocarpine-induced status epilepticus and subsequent neuronal damage in rats.

Experiments were conducted to evaluate the effects of transcranial focal electrical stimulation (TFS) applied via tripolar concentric ring electrodes, alone and associated with a sub-effective dose of diazepam (DZP) on the expression of status epilepticus (SE) induced by lithium-pilocarpine (LP) and subsequent neuronal damage in the hippocampus. Immediately before pilocarpine injection, male Wistar rats received TFS (300Hz, 200-µs biphasic square charge-balanced 50-mA constant current pulses for 2min) alone or combined with a sub-effective dose of DZP (0.41mg/kg, i.p.). In contrast with DZP or TFS alone, DZP plus TFS reduced the incidence of, and enhanced the latency to, mild and severe generalized seizures and SE induced by LP. These effects were associated with a significant reduction in the number of degenerated neurons in the hippocampus. The present study supports the notion that TFS combined with sub-effective doses of DZP may represent a therapeutic tool to induce anticonvulsant effects and reduce the SE-induced neuronal damage.

Study of the Long-Term Aging of Polypropylene-Made Disposable Surgical Masks and Filtering Facepiece Respirators.

The main purpose of this work is to contribute to understanding the mechanism of oxidation of the polymeric components of common disposable masks used during the COVID-19 pandemic to offer the chemical basis to understand their long-term behavior under typical environmental conditions. Artificial aging of representative mask layers under isothermal conditions (110 °C) or accelerated photoaging showed that all the PP-made components underwent a fast oxidation process, following the typical hydrocarbon oxidation mechanism. In particular, yellowing and the melting temperature drop are early indicators of their diffusion-limited oxidation. Morphology changes also induced a loss of mechanical properties, observable as embrittlement of the fabric fibers. Results were validated through preliminary outdoor aging of masks, which allows us to predict they will suffer fast and extensive oxidation only in the case of contemporary exposure to sunlight and relatively high environmental temperature, leading to their extensive breakdown in the form of microfiber fragments, i.e., microplastics.