Changes in Accommodative and Binocular Function following Phakic Intraocular Lens for High and Low-to-Moderate Myopia.

The aim was to evaluate accommodative and binocular function of phakic intraocular lens implantable collamer lens (ICL) in high and low-to-moderate myopia. Prospective comparative cohort study with 38 myopic patients who underwent ICL implantation were divided into two groups of 19 patients, each one based on the spherical equivalent (SE): high-power (SE ≤ −6 D) and low-to-moderate (SE > −6 D). The push-up amplitude of accommodation (AA), monocular accommodative facility (MAF), distance and near ocular deviation, near convergence amplitude, near point convergence (NPC), stereopsis, and accommodative convergence/accommodation (AC/A) ratio were assessed before surgery and 1 week and 1 month postoperatively. The mean residual refractive error at 1 month after surgery improved in both groups, 0.18 ± 0.34 D and 0.09 ± 0.26 D, respectively (p < 0.001). There was a significant decrease in AA in both groups between preoperatively and at 1-week (p = 0.001; p = 0.008, respectively) and 1-month follow-up (p = 0.001; p = 0.008). For the rest of the binocular measurements, no statistically significant postoperative changes were found in any group. This finding suggests follow-up studies on amplitude of accommodation in phakic intraocular lens ICL implantation.

Neuromodulation of Astrocytic K+ Clearance.

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

Generating Brain Waves, the Power of Astrocytes.

Synchronization of neuronal activity in the brain underlies the emergence of neuronal oscillations termed "brain waves", which serve various physiological functions and correlate with different behavioral states. It has been postulated that at least ten distinct mechanisms are involved in the formulation of these brain waves, including variations in the concentration of extracellular neurotransmitters and ions, as well as changes in cellular excitability. In this mini review we highlight the contribution of astrocytes, a subtype of glia, in the formation and modulation of brain waves mainly due to their close association with synapses that allows their bidirectional interaction with neurons, and their syncytium-like activity via gap junctions that facilitate communication to distal brain regions through Ca2+ waves. These capabilities allow astrocytes to regulate neuronal excitability via glutamate uptake, gliotransmission and tight control of the extracellular K+ levels via a process termed K+ clearance. Spatio-temporal synchrony of activity across neuronal and astrocytic networks, both locally and distributed across cortical regions, underpins brain states and thereby behavioral states, and it is becoming apparent that astrocytes play an important role in the development and maintenance of neural activity underlying these complex behavioral states.

Dynamic interplay between H-current and M-current controls motoneuron hyperexcitability in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a type of motor neuron disease (MND) in which humans lose motor functions due to progressive loss of motoneurons in the cortex, brainstem, and spinal cord. In patients and in animal models of MND it has been observed that there is a change in the properties of motoneurons, termed neuronal hyperexcitability, which is an exaggerated response of the neurons to a stimulus. Previous studies suggested neuronal excitability is one of the leading causes for neuronal loss, however the factors that instigate excitability in neurons over the course of disease onset and progression are not well understood, as these studies have looked mainly at embryonic or early postnatal stages (pre-symptomatic). As hyperexcitability is not a static phenomenon, the aim of this study was to assess the overall excitability of upper motoneurons during disease progression, specifically focusing on their oscillatory behavior and capabilities to fire repetitively. Our results suggest that increases in the intrinsic excitability of motoneurons are a global phenomenon of aging, however the cellular mechanisms that underlie this hyperexcitability are distinct in SOD1G93A ALS mice compared with wild-type controls. The ionic mechanism driving increased excitability involves alterations of the expression levels of HCN and KCNQ channel genes leading to a complex dynamic of H-current and M-current activation. Moreover, we show a negative correlation between the disease onset and disease progression, which correlates with a decrease in the expression level of HCN and KCNQ channels. These findings provide a potential explanation for the increased vulnerability of motoneurons to ALS with aging.

Astrocytic modulation of cortical oscillations.

Brain waves are rhythmic voltage oscillations emerging from the synchronization of individual neurons into a neuronal network. These oscillations range from slow to fast fluctuations, and are classified by power and frequency band, with different frequency bands being associated with specific behaviours. It has been postulated that at least ten distinct mechanisms are required to cover the frequency range of neural oscillations, however the mechanisms that gear the transition between distinct oscillatory frequencies are unknown. In this study, we have used electrophysiological recordings to explore the involvement of astrocytic K+ clearance processes in modulating neural oscillations at both network and cellular levels. Our results indicate that impairment of astrocytic K+ clearance capabilities, either through blockade of K+ uptake or astrocytic connectivity, enhance network excitability and form high power network oscillations over a wide range of frequencies. At the cellular level, local increases in extracellular K+ results in modulation of the oscillatory behaviour of individual neurons, which underlies the network behaviour. Since astrocytes are central for maintaining K+ homeostasis, our study suggests that modulation of their inherent capabilities to clear K+ from the extracellular milieu is a potential mechanism to optimise neural resonance behaviour and thus tune neural oscillations.

A small-molecule TrkB ligand restores hippocampal synaptic plasticity and object location memory in Rett syndrome mice.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are reduced in RTT autopsy brains and in multiple brain areas of Mecp2-deficient mice. Furthermore, experimental interventions that increase BDNF levels improve RTT-like phenotypes in Mecp2 mutant mice. Here, we characterized the actions of a small-molecule ligand of the BDNF receptor TrkB in hippocampal function in Mecp2 mutant mice. Systemic treatment of female Mecp2 heterozygous (HET) mice with LM22A-4 for 4 weeks improved hippocampal-dependent object location memory and restored hippocampal long-term potentiation (LTP). Mechanistically, LM22A-4 acts to dampen hyperactive hippocampal network activity, reduce the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs), and reduce the frequency of spontaneous tetrodotoxin-resistant Ca2+ signals in Mecp2 mutant hippocampal neurons, making them comparable to those features observed in wild-type neurons. Together, these observations indicate that LM22A-4 is a promising therapeutic candidate for the treatment of hippocampal dysfunction in RTT.

Astrocytic modulation of neuronal excitability through K+ spatial buffering.

The human brain contains two major cell populations, neurons and glia. While neurons are electrically excitable and capable of discharging short voltage pulses known as action potentials, glial cells are not. However, astrocytes, the prevailing subtype of glia in the cortex, are highly connected and can modulate the excitability of neurons by changing the concentration of potassium ions in the extracellular environment, a process called K+ clearance. During the past decade, astrocytes have been the focus of much research, mainly due to their close association with synapses and their modulatory impact on neuronal activity. It has been shown that astrocytes play an essential role in normal brain function including: nitrosative regulation of synaptic release in the neocortex, synaptogenesis, synaptic transmission and plasticity. Here, we discuss the role of astrocytes in network modulation through their K+ clearance capabilities, a theory that was first raised 50 years ago by Orkand and Kuffler. We will discuss the functional alterations in astrocytic activity that leads to aberrant modulation of network oscillations and synchronous activity.

Prolonged Incubation of Acute Neuronal Tissue for Electrophysiology and Calcium-imaging.

Acute neuronal tissue preparations, brain slices and retinal wholemount, can usually only be maintained for 6 - 8 h following dissection. This limits the experimental time, and increases the number of animals that are utilized per study. This limitation specifically impacts protocols such as calcium imaging that require prolonged pre-incubation with bath-applied dyes. Exponential bacterial growth within 3 - 4 h after slicing is tightly correlated with a decrease in tissue health. This study describes a method for limiting the proliferation of bacteria in acute preparations to maintain viable neuronal tissue for prolonged periods of time (>24 h) without the need for antibiotics, sterile procedures, or tissue culture media containing growth factors. By cycling the extracellular fluid through UV irradiation and keeping the tissue in a custom holding chamber at 15 - 16 °C, the tissue shows no difference in electrophysiological properties, or calcium signaling through intracellular calcium dyes at >24 h postdissection. These methods will not only extend experimental time for those using acute neuronal tissue, but will reduce the number of animals required to complete experimental goals, and will set a gold standard for acute neuronal tissue incubation.

La influencia del estrés o ansiedad de la gestante en el peso fetal o neonatal: revisión bibliográfica / Impact of maternal stress or anxiety on the fetal or neonatal weight: a literature review

Objetivo: Examinar si la presencia de ansiedad o estrés materno durante el embarazo influye en el peso del feto o el neonato y cómo cambian las variables asociadas. Metodología: Se llevó a cabo una revisión bibliográfica de artículos indexados en las bases de datos PubMed, CINHAL, Cuiden, Scielo, Lilacs, Dialnet, Latindex, Cuidatge y WorldCat, publicados entre 2001 y 2016. Resultados: A pesar de que la metodología de los estudios es muy variada, 9 de los 22 artículos seleccionados para la revisión concluyeron que existe una relación entre la presencia de estrés o ansiedad y el menor peso del bebé al nacer. No hay consenso sobre en qué trimestre de gestación afecta más el estrés, aunque sí se destaca la importancia del segundo trimestre. Conclusión: La evidencia indica que la presencia de estrés o ansiedad durante el embarazo afecta negativamente al peso fetal o del recién nacido, reduciéndolo o impidiendo que se desarrolle el potencial de éste. La disparidad de herramientas y momento de medida del estrés o la ansiedad, entre otras variables, puede influir en la lectura de los resultados (AU)

Objective: To clarify through a review of the evidence whether the presence of stress or anxiety during pregnancy influence fetal weight and how change the associated variables. Methods: A literature search was conducted on PubMed, CINHAL, Cuiden, Scielo, Lilacs, Dialnet, Latindex, Cuidatge and Worldcat databases for articles published between 2001 and 2016 in peer-reviewed journals. Results: A total of 9 articles conclude that the babies of anxious and stressed women born weighing less despite there are multiples differences on the methodology of each article. There is no consensus about which trimester of pregnancy is more critical nor the mechanisms involved on the weight although emphasize the second trimester of pregnancy. Conclusions: The evidence shows that the presence of stress during pregnancy is related to a reduction on the birthweight. The disparity measurement tools and time stress, among other variables, may affect the reading of the results (AU)

Caracterización de los factores de riesgo materno asociados al bajo peso al nacer. Isla de la Juventud. Abril 2007- Abril 2009 / Description of motherly risky factors associated to low weight newborn babies. Isle of Youth. April 2007- April 2009

Se realizó estudio descriptivo retrospectivo para caracterizar el comportamiento de los factores de riesgo maternos relacionados con la aparición del bajo peso al nacer en la Isla de la Juventud en el período abril 2007 a abril 2009. La muestra estuvo integrada por 141 gestantes, que tuvieron como producto final un recién nacido bajo peso al nacer en el período estudiado. Se utilizó el método de porcentajes para el estudio de las variables mediante tablas estadísticas. Hubo predominio en madres menores de 20 años, las que comenzaron la gestación con bajo peso u obesidad y las fumadoras. La Hipertensión Arterial Crónica y la Diabetes Mellitus pre-gestacional fueron las condiciones maternas asociadas con mayor frecuencia al inicio de la gestación. Así mismo, fueron la prematuridad, la anemia y la ganancia insuficiente de peso las complicaciones más frecuentes encontradas en la muestra durante el período gravídico(AU)