INTEGRATIVE CENTRAL NERVOUS SYSTEM ACTIVITY OF RATS IN GERONTOGENESIS UNDER EXPERIMENTAL HYPERGLYCEMIA

Diabetes mellitus has a major impact on the brain and its cognitive function. The pathogenesis of these disorders is still not well understood. Therefore, it is necessary to find ways of solving these manifestations in hyperglycemia in order to prevent the risk of complications that will lead to a worsening of living conditions. In the experiment, the state of conditioned-reflex and orientation-research activity of rats of different ages (middle-aged rats and old rats) in conditions of experimental hyperglycemia was found. The animals were kept under standard vivarium conditions. Experimental hyperglycemia was modeled by intraperitoneal solution injection of alloxan monohydrate (120 mg/kg body weight, Sigma). For 10 days, blood glucose was determined using a portable glucometer «Bionime». On day 10, those animals were selected that had a blood glucose value above 28 mmol/L. The analysis of orientation-research and emotional activity was carried out using the «Open Field» technique. The number of squares crossed, the number of lifts on the hind legs, the number of peeking into the burrows, grooming, and the number of bowel movements were recorded. The conditioned passive avoidance technique was used to study the stable and labile phases of memory. In both age groups, the indicators of orientation-research activity differed significantly (p < 0.05). The decrease in the number of squares crossed, the number of racks up and the study of minks was more pronounced in middle-aged animals with diabetes mellitus. The increase in the number of amnesiac animals was also more pronounced in the middle-aged rats of the research group. A decrease in the latency period was noted in both age groups. Thus, it was found that experimental hyperglycemia had pronounced consequences for the cognitive function of animals, respectively, diabetes mellitus has a negative effect on the brain.

Contrasting effects of Western vs. Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model

Dietary changes associated with industrialization substantially increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease, major contributors to the public health burden. The high prevalence of these chronic diseases is often attributed to an 'evolutionary mismatch' between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout human evolutionary history (e.g., simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to ancestral human hunter-gatherer diets, such as a Mediterranean diet. Peripheral blood monocytes, precursors to macrophages and important mediators of innate immunity and inflammation, are sensitive to the environment and may represent a critical intermediate in the pathway linking diet to disease. We evaluated the effects of 15 months of whole diet manipulations mimicking human Western or Mediterranean diet patterns on monocyte polarization using a well-established model of human health, the cynomolgus macaque (Macaca fascicularis). Monocyte transcriptional profiles differed markedly between the two diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. Compared to the Mediterranean diet, the Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered behavior. For example, Western-fed individuals were more anxious and less socially integrated compared to the Mediterranean-fed subjects. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. The results of this study provide new insights into evolutionary mismatch at the molecular level and uncover new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.

Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery

Allopregnanolone, a positive modulator of GABAA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED50, 5.6 mg/kg), picrotoxin (ED50, 5.9 mg/kg), and bicuculline seizure tests. The effect peaked at 15 min, decayed over 1 h, and was still evident in some experiments at 6 h. Intranasal allopregnanolone also delayed the onset of seizures in the maximal PTZ test. At an allopregnanolone dose (16 mg/kg) that conferred comparable effects on seizure threshold as the benzodiazepines midazolam and diazepam (both at doses of 1 mg/kg), allopregnanolone caused minimal sedation or motor toxicity in the horizontal screen test whereas both benzodiazepines produced marked behavioral impairment. In addition, intranasal allopregnanolone failed to cause loss-of-righting reflex in most animals, but when the same dose was administered intramuscularly, all animals became impaired. Intranasal allopregnanolone (10 mg/kg) caused a rapid increase in brain allopregnanolone with a Tmax of ~5 min after initiation of the intranasal delivery. High levels of allopregnanolone were recovered in the olfactory bulb (Cmax, 16,000 ng/mg) whereas much lower levels (Cmax, 670 ng/mg) were present in the remainder of the brain. We conclude that the unique ability of intranasal allopregnanolone to protect against seizures without inducing behavioral adverse effects is due in part to direct nose-to-brain delivery, with preferential transport to brain regions relevant to seizures. Benzodiazepines are commonly administered intranasally for acute seizure therapy, including for the treatment of acute repetitive seizures, but are not transported from nose-to-brain. Intranasal allopregnanolone acts with greater speed, has less propensity for adverse effects, and has the ability to overcome benzodiazepine refractoriness. This is the first study demonstrating rapid functional central nervous system activity of a nose-to-brain-delivered steroid. Intranasal delivery circumvents the poor oral bioavailability of allopregnanolone providing a route of administration permitting its evaluation as a treatment for diverse neuropsychiatric indications.

Analgesia in the intensive care unit

Background. Sedation is a technique of using drugs to put a patient in a condition in which he can tolerate unpleasant procedures, while maintaining cardiorespiratory function. The main problems associated with analgesia and sedation (AS) are associated with the development of hypoxia, vomiting and aspiration, hypotension and hemodynamic instability, apnea. Objective. To describe the features of the modern AS. Materials and methods. Analysis of literature data on this issue. Results and discussion. AS can be performed with the help of different drugs. Benzodiazepines (preferably midazolam) and/or propofol in combination with low doses of opioids should be used in patients with concomitant cardiac abnormalities. The use of propofol in this category of patients is carried out by fractional administration (on average, 50 mg) with an interval of 30-40 seconds until an adequate sedative effect is achieved. Dexmedetomidine has been suggested as an adjuvant. It should be kept in mind that benzodiazepines are not suitable for creating a long-lasting sedative effect, and can cause paradoxical agitation in the elderly. Features of sedation in patients at risk of obstructive sleep apnea syndrome are represented with the use of a minimum dose of hypnotics without the use of opioids. Dexmedetomidine is considered as an alternative. It is advisable to use continuous positive airways pressure by inhalation of oxygen through the nasal cannula. Patients with morbid obesity should avoid lying on their back. For the effective control of airway patency, it is advisable to use endotracheal intubation. It is recommended to avoid long-acting drugs and drugs that cause respiratory depression. The use of propofol in this group is often associated with respiratory complications, so the use of remifentanil and dexmedetomidine is recommended as an alternative. For patients with chronic renal failure, midazolam and/or fentanyl should be preferred, however, the cardiovascular and pulmonary side effects of any of these drugs are exacerbated when they are used concomitantly. In patients with hepatic dysfunction, midazolam may exacerbate symptoms, so propofol should be preferred. If the latter is used, the doctor should be near the patient throughout the procedure and monitor him exclusively. As for dexmedetomidine, this drug selectively binds and activates presynaptic α2-adrenoreceptors, inhibiting the release of norepinephrine. As a result, postsynaptic activation of adrenoceptors is inhibited, sympathetic activity is suppressed, leading to analgesia, sedation and decrease of anxiety. Under conditions of mild or moderate sedation caused by dexmedetomidine, patients respond to verbal stimulation and are able to communicate and cooperate with medical staff, and after awakening show high results in tests of central nervous system activity. Dexmedetomidine is less likely to cause postoperative delirium than midazolam (54 % vs. 76.6 %) and does not adversely affect sleep quality, unlike propofol. Dexmedetomidine can be used together with paracetamol. Intravenous paracetamol significantly reduces postoperative pain and the need for opioids. Conclusions. 1. AS can be performed with the use of benzodiazepines, propofol, dexmedetomidine. 2. Benzodiazepines are not suitable for creating a long-lasting sedative effect, and can cause paradoxical agitation in the elderly. 3. Patients with different comorbid conditions are characterized by different features of required AS. 4. Dexmedetomidine gives the patient the opportunity to communicate and cooperate with medical staff, rarely causes postoperative delirium and does not adversely affect the sleep quality. 5. Intravenous paracetamol significantly reduces postoperative pain and the need for opioids.

Normative data and correlation between dynamic knee valgus and neuromuscular response among healthy active males: a cross-sectional study

The dynamic knee valgus (DKV) during different sport maneuvers has been widely described as risk factor to develop an anterior cruciate ligament injury. Hip and knee muscles seem to have a crucial role to prevent the dynamic knee valgus. This study aimed to give normative and correlational data about DKV and hip and knee neuromuscular response (NMR) among healthy active males. The hypothesis is that DKV could be correlated with hip NMR. A cross-sectional correlational study. Research Anatomy Laboratory. The study was carried out among 50 active, non-injured males. Dynamic Knee-Valgus angle and lower limb posterior chain muscles Neuromuscular Response. DKV was measured using Kinovea software during a Single-Legged Drop Jump test and NMR was measured using tensiomyography and myotonometry for gluteus maximum, biceps femoris, semitendinosus, lateral and medial gastrocnemius. Right and left limbs were both performed and analyzed independently. No significant correlation was observed between DKV and hip and knee muscles NMR. This study shows normative and correlational data about dynamic knee valgus, tensiomyography and myotonometry for healthy and active males. The DKV control seems to be non-correlated with isolated hip and knee muscles NMR so this suggests it is more about Central Nervous System activity than about isolated muscles NMR.

A systematic review of caregiver–child physiological synchrony across systems: Associations with behavior and child functioning

Extensive research has established a positive association between caregiver-child behavioral synchrony and child developmental functioning. Burgeoning research examining physiological synchrony has yet to elucidate its impact for children’s developing self-regulation. The objectives of this systematic review were to: 1) determine whether there is evidence that caregiver-child physiological synchrony promotes positive child development, 2) examine developmental differences in physiological synchrony and its correlates, and 3) explore whether context, risk, and/or stress influence patterns of synchrony. Sixty-nine studies met the following criteria on PubMed and PsycINFO: 1) peer-reviewed empirical articles in English that 2) examine autonomic, hypothalamic-pituitary-adrenocortical, and/or central nervous system activity 3) for caregivers and children 4) in response to a task and 5) directly examine the association between caregiver and child physiology. Findings varied based on developmental period and current behavioral context. Functional differences may exist across physiological systems and contexts. Synchrony may have different developmental consequences for dyads with and without certain risk factors. Few studies examine physiological synchrony across multiple systems or contexts, nor do they measure child characteristics associated with synchrony. Statistical and methodological challenges impede interpretation. Findings generally support the idea that physiological synchrony may support children’s developing self-regulation. Longitudinal research is needed to examine child developmental outcomes over time.

Differences in Activity of the Brain Networks During Voluntary Motor Tasks Engaging the Local and Global Muscular Systems of the Lower Trunk

Low back pain constitutes a multidimensional problem of largely unknown origin. One of the recent theories explaining its frequent occurrence includes speculative statements on patterns of central nervous system activity associated with the control of so-called local and global muscles of the lower trunk. The objective of the study was to verify whether there is a difference in the activity of the brain during selective, voluntary contraction of the local and global abdominal muscles as assessed by functional MRI. Twenty healthy subjects participated. An experimental design was applied with repeated measurements of the blood-oxygen-level–dependent signal from the brain during voluntary contraction of the local and global abdominal muscles, performed in random order. Prior to registration, a 2-week training period was introduced, aiming to master the experimental motor tasks. The magnetic resonance imaging (MRI) data were processed using the FMRIB Software Library (Oxford, UK). Brain areas showing significant activations/deactivations were identified and averaged across all participants, and intercondition differential maps were computed. Areas of significant intercondition differences were linked to the corresponding anatomical structures and ascribed to the default mode functional brain network and to the sensorimotor network. Contraction of the local abdominal muscles elicited more pronounced activity of the brain cortex, basal ganglia, and cerebellum. This suggests that motor control of the abdominal musculature consists of two modes of brain activity and that control of the local muscles may be a more challenging task for the brain. Moreover, contraction of the local muscles elicited more distinct deactivation of the default mode network, which may have implications for diagnostics and therapy of low back pain.

Age-related differences in Autonomic/Central Coupling during a Daytime Nap

Age-dependent functional changes are mirrored by declines in both the central nervous system (CNS) and in the autonomic nervous system (ANS) and have been related to pathological aging. Prior studies have demonstrated inter-dependence between central and autonomic events that contribute to cognition. Moreover, our group recently identified a temporal coupling of Autonomic and Central Events (ACEs) during sleep using electrocardiogram (ECG) to measure heart rate and electroencephalography (EEG) to measure sleeping brain rhythms [40]. We showed that heart rate bursts (HRBs) temporally coincided with increased slow wave activity (SWA, 0.5-1Hz) and sigma activity (12-15Hz), followed by parasympathetic surge (RRHF) during non-rapid eye movement (NREM) sleep. Given that there are paralleling age-related declines in both the ANS and CNS, the current study investigated how these declining systems impact ACE coupling during daytime naps in older and younger adults. Despite, lower overall EEG activity during ACE windows in older adults, both younger and older adults showed HRB-modulated increases in SWA and sigma during wake and N2. However, older adults did not show the same pattern during N3. Furthermore, while younger adults demonstrated a RRHF increase only after HRBs, older adults showed an earlier rise and maintenance of the RRHF. Taken together, our results demonstrated that ACE activity remains generally intact with age. Given that age-related deterioration in autonomic and central nervous system activity is implicated in pathological decline, the general maintenance of alignment between the two systems is intriguing and may facilitate novel insights to aging.Statement of SignificanceInteractions between the CNS and ANS and have emerged as one of the key markers for health and cognition. Given that both declines in ANS and CNS have been independently implicated with pathological aging and mortality, it’s pressing to understand how the CNS-ANS interactions change with age. Here, we examined the temporal coupling during wake and sleep among young and older adults during a daytime nap. Similar coupling was demonstrated during wake and N2, with older adults showed less coupling in N2 compared to younger adults. Furthermore, older adults showed no coupling during N3. The current study identifying declines CNS-ANS coupling may facilitate novel insights and provide new targets to combat neurodegenerative disease.