Single Low Dose of Cocaine–Structural Brain Injury Without Metabolic and Behavioral Changes

Chronic cocaine use has been shown to lead to neurotoxicity in rodents and humans, being associated with high morbidity and mortality rates. However, recreational use, which may lead to addictive behavior, is often neglected. This occurs, in part, due to the belief that exposure to low doses of cocaine comes with no brain damage risk. Cocaine addicts have shown glucose metabolism changes related to dopamine brain activity and reduced volume of striatal gray matter. This work aims to evaluate the morphological brain changes underlying metabolic and locomotor behavioral outcome, in response to a single low dose of cocaine in a pre-clinical study. In this context, a Balb-c mouse model has been chosen, and animals were injected with a single dose of cocaine (0.5 mg/kg). Control animals were injected with saline. A behavioral test, positron emission tomography (PET) imaging, and anatomopathological studies were conducted with this low dose of cocaine, to study functional, metabolic, and morphological brain changes, respectively. Animals exposed to this cocaine dose showed similar open field activity and brain metabolic activity as compared with controls. However, histological analysis showed alterations in the prefrontal cortex and hippocampus of mice exposed to cocaine. For the first time, it has been demonstrated that a single low dose of cocaine, which can cause no locomotor behavioral and brain metabolic changes, can induce structural damage. These brain changes must always be considered regardless of the dosage used. It is essential to alert the population even against the consumption of low doses of cocaine.

Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (Tdelta +0.18°C, IQR −0.01 – 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate ( p = 0.003) and CMD-lactate ( p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, Tdelta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher Tdelta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH.

Interregional causal influences of brain metabolic activity reveal the spread of aging effects during normal aging

During healthy brain aging, different brain regions show anatomical or functional declines at different rates, and some regions may show compensatory increases in functional activity. However, few studies have explored interregional influences of brain activity during the aging process. We proposed a causality analysis framework combining high dimensionality independent component analysis (ICA), Granger causality, and LASSO (least absolute shrinkage and selection operator) regression on longitudinal brain metabolic activity data measured by Fludeoxyglucose positron emission tomography (FDG-PET). We analyzed FDG-PET images from healthy old subjects, who were scanned for at least five sessions with an averaged intersession interval of about one year. The longitudinal data were concatenated across subjects to form a time series, and the first order autoregressive model was used to measure interregional causality among the independent sources of metabolic activity identified using ICA. Several independent sources with reduced metabolic activity in aging, including the anterior temporal lobe and orbital frontal cortex, demonstrated causal influences over many widespread brain regions. On the other hand, the influenced regions were more distributed, and had smaller age related declines or even relatively increased metabolic activity. The current data demonstrated interregional spreads of aging on metabolic activity at the scale of a year, and have identified key brain regions in the aging process that have strong influences over other regions.

Non-thermal microwave radiation-induced brain tissue dehydration as a potential factor for brain functional impairment

Based on our previous finding that metabolically controlled cell hydration is sensitive to the changes of physicochemical properties of cell aqua medium, which take place upon the effect of weak physical signals, including microwaves with non-thermal intensity (NT MW), it has been hypothesized that cell aqua medium serves as a primary target for NT MW effect on brain tissue. To elucidate the nature of the metabolic pathway through which the effect of NT MW-induced changes of physicochemical properties of cell aqua medium modulate cell hydration, the effects of intraperitoneal (IP) injection of PS treated by NT MW on brain tissue hydration, 45Ca2+ uptake, [3H]-ouabain binding with cell membrane and intracellular cyclic nucleotides have been studied. The obtained data indicate that PS treated by NT MW through the activation of high affinity ouabain receptors in membrane stimulates cAMP-dependent Na+/Ca2+ exchange in reverse mode (R), which leads to brain tissue hydration in healthy (young) and dehydration in non-healthy (old) rats.As NT MW radiation-induced activation of R Na+/Ca2+ exchange leads to the increase of intracellular Ca2+ ([Ca2+]i), it is considered as a potential factor leading to the brain functional impairment, especially when brain metabolic activity is depressed (e.g. during aging).