Long-term deficits in cortical circuit function after asphyxial cardiac arrest and resuscitation in developing rats

AbstractCardiac arrest is a common cause of global hypoxic-ischemic brain injury. Poor neurologic outcome among cardiac arrest survivors results not only from direct cellular injury but also from subsequent long-term dysfunction of neuronal circuits. Here, we investigated the long-term impact of cardiac arrest during development on the function of cortical layer IV (L4) barrel circuits in the rat primary somatosensory cortex. We used multielectrode single-neuron recordings to examine responses of presumed excitatory L4 barrel neurons to controlled whisker stimuli in adult (8 ± 2-mo-old) rats that had undergone 9 min of asphyxial cardiac arrest and resuscitation during the third postnatal week. Results indicate that responses to deflections of the topographically appropriate principal whisker (PW) are smaller in magnitude in cardiac arrest survivors than in control rats. Responses to adjacent whisker (AW) deflections are similar in magnitude between the two groups. Because of a disproportionate decrease in PW-evoked responses, receptive fields of L4 barrel neurons are less spatially focused in cardiac arrest survivors than in control rats. In addition, spiking activity among L4 barrel neurons is more correlated in cardiac arrest survivors than in controls. Computational modeling demonstrates that experimentally observed disruptions in barrel circuit function after cardiac arrest can emerge from a balanced increase in background excitatory and inhibitory conductances in L4 neurons. Experimental and modeling data together suggest that after a hypoxic-ischemic insult, cortical sensory circuits are less responsive and less spatially tuned. Modulation of these deficits may represent a therapeutic approach to improving neurologic outcome after cardiac arrest.</jats:p

Thalamocortical dysfunction and thalamic injury after asphyxial cardiac arrest in developing rats

Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic Reticular Nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on post-natal day 17. We found that 48–72 hours after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6–8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine min of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the Reticular Nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest

Прогнозирование влияния фотодинамической терапии на выживаемость у пациентов с IV стадией злокачественных новообразований поджелудочной железы

The article presents the results of a study of survival after complex palliative treatment of patients with malignant tumors of the pancreas stage IV in two comparable groups of patients. The aim of the study is to determine the prognostic factors affecting survival in patients with stage IV pancreatic cancer who received local and systemic photodynamic therapy. In the main group, which consisted of 19 patients with histologically veried stage IV pancreatic maligant tumor, palliative treatment was performed using photodynamic therapy. In the comparison group, consisting of 28 patients with histologically veried malignant tumor of the pancreas stage IV, palliative treatment was performed without the use of photodynamic therapy. On the background of the use of local and systemic photodynamic therapy in the main group it was observed a statistically significant increase in life expectancy compared with the comparison group. The three-month survival of patients who received local and systemic photodynamic therapy is affected by the level of brinogen before treatment. The level of brinogen above 3.4 g/l makes it possible to predict a decrease in the probability of three-month survival after photodynamic therapy. Thus, complex treatment with the use of photodynamic therapy for stage IV malignant tumors of the pancreas can increase the survival rate of patients.В работе представлены результаты исследования выживаемости в двух сопоставимых группах больных после комплексного паллиативного лечения больных со злокачественными новообразованиями поджелудочной железы IV стадии. Целью исследования было определить прогностические факторы, влияющие на выживаемость у больных IV стадией злокачественного новообразования поджелудочной железы, которым планируется проведение локальной и системной фотодинамической терапии. В основной группе, включавшей 19 пациентов с гистологически верифицированным злокачественным новообразованием поджелудочной железы IV стадии, проводили паллиативное лечение с применением фотодинамической терапии. В группе сравнения, включавшей 28 пациентов с гистологически верифицированным злокачественным новообразованием поджелудочной железы IV стадии, проводили паллиативное лечение без применения фотодинамической терапии. На фоне применения локальной и системной фотодинамической терапии в основной группе наблюдали статистически значимое увеличение продолжительности жизни по сравнению с группой сравнения. Исследования показали, что на трехмесячную выживаемость пациентов, которым планируется проведение локальной и системной фотодинамической терапии, влияет уровень фибриногена до лечения. Уровень фибриногена выше 3,40 г/л позволяет прогнозировать снижение вероятности трехмесячной выживаемости после проведения фотодинамической терапии. Таким образом, комплексное лечение с применением фотодинамической терапии злокачественных новообразований поджелудочной железы IV стадии позволяет увеличить выживаемость пациентов

Stimulus Dependence of Barrel Cortex Directional Selectivity

Neurons throughout the rat vibrissa somatosensory pathway are sensitive to the angular direction of whisker movement. Could this sensitivity help rats discriminate stimuli? Here we use a simple computational model of cortical neurons to analyze the robustness of directional selectivity. In the model, directional preference emerges from tuning of synaptic conductance amplitude and latency, as in recent experimental findings. We find that directional selectivity during stimulation with random deflection sequences is strongly dependent on the mean deflection frequency: Selectivity is weakened at high frequencies even when each individual deflection evokes strong directional tuning. This variability of directional selectivity is due to generic properties of synaptic integration by the neuronal membrane, and is therefore likely to hold under very general physiological conditions. Our results suggest that directional selectivity depends on stimulus context. It may participate in tasks involving brief whisker contact, such as detection of object position, but is likely to be weakened in tasks involving sustained whisker exploration (e.g., texture discrimination)

Особенности течения хронической обструктивной болезни легких у больных сахарным диабетом

Fifty-two patients with chronic obstructive pulmonary disease (COPD) aged 44 to 71 yrs were examined. Of them, 26 ones suffered from type 2 diabetes mellitus (DM). We established that in patients with concomitant DM, COPD has more severe course with more advanced respiratory failure and chronic cor pulmonale and more frequent exacerbations. COPD patients with concomitant DM more often have co-morbidity, such as obesity, ischemic heart disease, chronic heart failure. Co-morbidity of COLD and DM requires more extensive pharmacotherapy.Обследованы 52 больных хронической обструктивной болезнью легких (ХОБЛ) в возрасте от 44 лет до 71 года. Из них 26 пациентов страдали сахарным диабетом (СД) 2-го типа. Проводилось клинико-инструментальное обследование. Установлено, что на фоне СД ХОБЛ протекает тяжелее: более выражены дыхательная недостаточность и хроническое легочное сердце, чаще возникают обострения. У больных ХОБЛ на фоне СД выявлена высокая частота коморбидных заболеваний: ожирения, ишемической болезни сердца, хронической сердечной недостаточности. Сочетание ХОБЛ и СД требует большего объема фармакотерапии

Whisker Movements Reveal Spatial Attention: A Unified Computational Model of Active Sensing Control in the Rat

Spatial attention is most often investigated in the visual modality through measurement of eye movements, with primates, including humans, a widely-studied model. Its study in laboratory rodents, such as mice and rats, requires different techniques, owing to the lack of a visual fovea and the particular ethological relevance of orienting movements of the snout and the whiskers in these animals. In recent years, several reliable relationships have been observed between environmental and behavioural variables and movements of the whiskers, but the function of these responses, as well as how they integrate, remains unclear. Here, we propose a unifying abstract model of whisker movement control that has as its key variable the region of space that is the animal's current focus of attention, and demonstrate, using computer-simulated behavioral experiments, that the model is consistent with a broad range of experimental observations. A core hypothesis is that the rat explicitly decodes the location in space of whisker contacts and that this representation is used to regulate whisker drive signals. This proposition stands in contrast to earlier proposals that the modulation of whisker movement during exploration is mediated primarily by reflex loops. We go on to argue that the superior colliculus is a candidate neural substrate for the siting of a head-centred map guiding whisker movement, in analogy to current models of visual attention. The proposed model has the potential to offer a more complete understanding of whisker control as well as to highlight the potential of the rodent and its whiskers as a tool for the study of mammalian attention

Muscle atrophy in mechanically-ventilated critically ill children

10.1371/journal.pone.0207720PLoS ONE1312e020772

Muscle Atrophy in Mechanically-Ventilated Critically ill Children.

IMPORTANCE:ICU-acquired muscle atrophy occurs commonly and worsens outcomes in adults. The incidence and severity of muscle atrophy in critically ill children are poorly characterized. OBJECTIVE:To determine incidence, severity and risk factors for muscle atrophy in critically ill children. DESIGN, SETTING AND PARTICIPANTS:A single-center, prospective cohort study of 34 children receiving invasive mechanical ventilation for ≥48 hours. Patients 1 week- 18 years old with respiratory failure and without preexisting neuromuscular disease or skeletal trauma were recruited from a tertiary Pediatric Intensive Care Unit (PICU) between June 2015 and May 2016. We used serial bedside ultrasound to assess thickness of the diaphragm, biceps brachii/brachialis, quadriceps femoris and tibialis anterior. Serial electrical impedance myography (EIM) was assessed in children >1 year old. Medical records were abstracted from an electronic database. EXPOSURES:Respiratory failure requiring endotracheal intubation for ≥48 hours. MAIN OUTCOME AND MEASURES:The primary outcome was percent change in muscle thickness. Secondary outcomes were changes in EIM-derived fat percentage and "quality". RESULTS:Of 34 enrolled patients, 30 completed ≥2 ultrasound assessments with a median interval of 6 (IQR 6-7) days. Mean age was 5.42 years, with 12 infants 1 year old (60%). In the entire cohort, diaphragm thickness decreased 11.1% (95%CI, -19.7% to -2.52%) between the first two assessments or 2.2%/day. Quadriceps thickness decreased 8.62% (95%CI, -15.7% to -1.54%) or 1.5%/day. Biceps (-1.71%; 95%CI, -8.15% to 4.73%) and tibialis (0.52%; 95%CI, -5.81% to 3.40%) thicknesses did not change. Among the entire cohort, 47% (14/30) experienced diaphragm atrophy (defined a priori as ≥10% decrease in thickness). Eighty three percent of patients (25/30) experienced atrophy in ≥1 muscle group, and 47% (14/30)-in ≥2 muscle groups. On multivariate linear regression, increasing age and traumatic brain injury (TBI) were associated with greater muscle loss. EIM revealed increased fat percentage and decreased muscle "quality". CONCLUSIONS AND RELEVANCE:In children receiving invasive mechanical ventilation, diaphragm and other skeletal muscle atrophy is common and rapid. Increasing age and TBI may increase severity of limb muscle atrophy. Prospective studies are required to link muscle atrophy to functional outcomes in critically ill children