Guanosine enhances glutamate uptake and oxidation, preventing oxidative stress in mouse hippocampal slices submitted to high glutamate levels.

Glutamate (Glu) is the main mammalian brain neurotransmitter. Concerning the glutamatergic neurotransmission, excessive levels of glutamate in the synaptic cleft are extremally harmful. This phenomenon, named as excitotoxicity is involved in various acute and chronic brain diseases. Guanosine (GUO), an endogenous guanine nucleoside, possesses neuroprotective effects in several experimental models of glutamatergic excitotoxicity, an effect accompanied by an increase in astrocytic glutamate uptake. Therefore, the objective of this study was to investigate the involvement of an additional putative parameter, glutamate oxidation to CO2, involved in ex-vivo GUO neuroprotective effects in mouse hippocampal slices submitted to glutamatergic excitotoxicity. Mice were sacrificed by decapitation, the hippocampi were removed and sliced. The slices were incubated for various times and concentrations of Glu and GUO. First, the concentration of Glu that produced an increase in L-[14C(U)]-Glu oxidation to CO2 without cell injury was determined at different time points (between 0 and 90 min); 1000 µM Glu increased Glu oxidation between 30 and 60 min of incubation without cell injury. Under these conditions (Glu concentration and incubation time), 100 µM GUO increased Glu oxidation (35%). Additionally, 100 µM GUO increased L-[3,4-3H]-glutamate uptake (45%) in slices incubated with 1000 µM Glu (0-30 min). Furthermore, 1000  µM Glu increased reactive species levels, SOD activity, and decreased GPx activity, and GSH content after 30 and 60 min; 100 µM GUO prevented these effects. This is the first study demonstrating that GUO simultaneously promoted an increase in the uptake and utilization of Glu in excitotoxicity-like conditions preventing redox imbalance.

Behavioral, Neurochemical and Brain Oscillation Abnormalities in an Experimental Model of Acute Liver Failure.

Hepatic encephalopathy (HE) represents a brain dysfunction caused by both acute and chronic liver failures, and its severity deeply affects the prognosis of patients with impaired liver function. In its pathophysiology, ammonia levels and glutamatergic system hyperactivity seem to play a pivotal role in the disruption of brain homeostasis. Here, we investigate important outcomes involved in behavioral performance, electroencephalographic patterns, and neurochemical parameters to better characterize the well-accepted animal model of acute liver failure (ALF) induced by subtotal hepatectomy (92% removal of tissue) that produces ALF. This study was divided into three cohorts: (1) rats clinically monitored after hepatectomy every 6 h for 96 h or until death; (2) rats tested in an open-field task (OFT) before and after surgery and had blood, cerebrospinal fluid, and brain tissue collected after the last OFT; and (3) rats that had continuous EEGs recorded before and after surgery for 3 days. The hepatectomized rats presented significant motor behavioral changes accompanied by important abnormalities in classical blood laboratory parameters of ALF, and EEG features suggestive of HE and deep disturbances in the brain glutamatergic system. Using an animal model of ALF induced via subtotal hepatectomy, this work provides a comprehensive and reliable experimental model that increases the opportunity for studying the effects of new treatment strategies to be explored in an unprecedented way. It also presents insights into the pathophysiology of HE in a reproducible model of ALF, which correlates important neurochemical and EEG aspects of the syndrome.

Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats.

Chronic stress, whether associated with obesity or not, leads to different neuroendocrine and psychological changes. Obesity or being overweight has become one of the most serious worldwide public health problems. Additionally, it is related to a substantial increase in daily energy intake, which results in substituting nutritionally adequate meals for snacks. This metabolic disorder can lead to morbidity, mortality, and reduced quality of life. On the other hand, brain-derived neurotrophic factor (BDNF) is widely expressed in all brain regions, particularly in the hypothalamus, where it has important effects on neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy metabolism. BDNF is involved in many activities modulated by the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect of obesity associated with chronic stress on the BDNF central levels of rats. Obesity was controlled by analyzing the animals' caloric intake and changes in body weight. As a stress parameter, we analyzed the relative adrenal gland weight. We found that exposure to chronic restraint stress during 12 weeks increases the adrenal gland weight, decreases the BDNF levels in the hippocampus and is associated with a decrease in the calorie and sucrose intake, characterizing anhedonia. These effects can be related stress, a phenomenon that induces depression-like behavior. On the other hand, the rats that received the hypercaloric diet had an increase in calorie intake and became obese, which was associated with a decrease in hypothalamus BDNF levels.

Accuracy of recorded body temperature of critically ill patients related to measurement site: a prospective observational study.

Accurate measurement of body temperature is an important indicator of the status of critically ill patients and is therefore essential. While axillary temperature is not considered accurate, it is still the conventional method of measurement in Asian intensive care units. There is uncertainty about the accuracy of thermometers for the critically ill. We compared the accuracy and precision of bladder, axillary and tympanic temperature measurements in critically ill patients. A total of 73 critically ill patients admitted to the intensive care unit of a teaching hospital were prospectively enrolled. Every four hours, we measured body temperature at three sites (bladder, axillary and tympanic). If the patient had received an indwelling pulmonary artery catheter, blood temperature was also recorded and this was compared with bladder, axillary and tympanic temperature readings. For all patients, axillary and tympanic temperature readings were compared with bladder temperature readings. Accuracy and precision were analysed using Bland-Altman analysis. When blood temperature data was available, the mean difference between blood and bladder temperature readings was small (0.02±0.21°C). Compared with bladder temperature, mean difference for axillary temperature was -0.33±0.55°C and for tympanic temperature it was -0.51±1.02°C. For critically ill patients, recorded axillary temperature was closer to bladder temperature than tympanic temperature.