Vol 11, No 3 (2017)

Remote ischemic conditioning (RIC) is a short-term treatment with ischemia–reperfusion of any organ or limb to increase the resistance of tissues to ischemic or other lesions or general resistance of the body. According to modern ideas, the cerebroprotective effects of RIC operate via the neurohumoral mechanisms, systems of the inflammatory response, and modulatory peptides. The intracellular regulatory and receptor systems, kinase cascades, and genome are also involved. Activation of these mechanisms prevents calcium, glutamate, and oxidant overload of neurons in the brain and opening of the mitochondrial pores, triggering of anti-apoptotic and anti-inflammatory processes, and maintenance of energy metabolism and synaptic plasticity. Based on literature data we conclude that RIC is a simple, cheap, and efficient method of neuroprotection with great translational potential.

Protein kinase B (Akt) is a key enzyme in one of many neuroprotective signaling cascades in neurons that are activated during preconditioning by episodes of moderate hypoxia/ischemia. However, the data on the involvement of this anti-apoptotic pathway in mechanisms of the hypoxic tolerance induced by different experimental protocols are incomplete and contradictory. We exposed rats to moderate hypobaric hypoxia (3MHH) corresponding to an altitude of 5000 m above sea level three times (once a day for 2 hours). The 3MHH treatment is known as an effective stimulus for hypoxic brain tolerance. We used immunocytochemistry to study the dynamics of phosphorylation of Akt caused by 3MHH in various areas of the brain. It was found that each of the three 3MHH episodes quickly (within 3 hours) activated Akt phosphorylation in the neocortex, piriform cortex, and dentate gyrus of the hippocampus. Severe hypobaric hypoxia (SHH), the equivalent of a rise to 11000 m above sea level, did not produce this effect. Behavioral experiments on 3MHH-preconditioned rats subjected to subsequent SHH have shown that blocking the activity of PI3K/Akt with wortmannin during preconditioning had an anxiogenic effect typical of non-preconditioned animals that survived the SHH. Thus, we established the details of the involvement of the PI3K/Akt pathway in the neuroprotective mechanism of 3MHH-preconditioning for the first time.

We performed an immunohistochemical study of histone H3 methylation at lysine 4 (H3K4medi+ tri) in the neurons of the hippocampus (CA3 area) and basolateral amygdala in rats with different levels of nervous system excitability under normal conditions and at different time points (24 hours, 2 weeks, and 2 months) after long-term emotional pain stress (LEPS). We found higher immunoreactivity of cells in both brain structures under normal conditions in the control groups of low-excitability rats of the HT strain in comparison with high-excitability rats of the LT strain. We describe the structural and temporal patterns of the influence of long-term emotional pain stress on the level of histone H3 methylation (K4), which depend on the excitability of the nervous system of the examined strains.

The objective of this study was to investigate the effects of 2,3,4-trimethoxy-N'-(8-metyl-8-azabicyclo[3.2.1.] octan-3-ylidene) benzohydrazide hydrochloride (LK-933), a compound of the tropane group with anxiolytic and antimigraine activity, on the levels of monoamines and their metabolites in different brain structures of outbred mice using HPLC–ED. Administration of LK-933 caused an increase in the composite characteristics that describe the rate of dopamine transformation into its metabolites dioxyphenylacetic acid and homovanillic acid in the frontal cortex by 114 and 181%, respectively. The levels of homovanillic acid in the same structure increased by 49%. These data implicate the dopaminergic pathway in the mechanism of LK-933 action.

This paper reports an analysis of the effects of sodium comenate on neurite growth from spinal ganglia under the conditions of hydrogen peroxide-induced oxidative stress and on the glutathione antioxidant system in the brain of mice exposed to immobilization stress. It has been demonstrated that sodium comenate at the concentrations of 0.1–0.001 mM stimulates the growth of neurites from spinal ganglia exposed to oxidative stress. The most profound stimulatory effect was observed with 0.001 mM sodium comenate. The administration of sodium comenate at doses of 1, 2, and 4 mg/kg contributed to the maintenance of the GSH content and glutathione peroxidase and glutathione reductase activities at the physiologically normal state level under stress conditions. The results of the study of neurotrophic and antioxidant effects of sodium comenate in oxidative stress suggest that this compound is a highly efficient neuroprotector.

We studied the postponed effect of neonatal proinflammatory stress (NPS) on the expression of the glucocorticoid receptor (GR) and the mineralcorticoid receptor (MR) in the dorsal (DH) and ventral hippocampus (VH) of female and male rats. We found that in male Wistar rats the expression of GR mRNA is higher in the DH than in the VH. Induction of NPS by administration of bacterial lipopolysaccharide (LPS) during the neonatal period differentially influenced the expression of GR mRNA in the DH and VH of 30-day-old animals. In males, LPS administration in the neonatal age increased GR expression in the VH and did not influence in the DH whereas, in females, it increased expression in the DH and did not influence in the VH. The expression of MR was not altered by NPS. Thus, NPS induces long-term changes in different parts of the hippocampus, which is considered as one of the key brain structures involved in the pathogeny of depressive disorder.