[Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer's disease].

INTRODUCTION: Alzheimer's disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI. MATERIAL AND METHODS: 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein-Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity. RESULTS: The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD. DISCUSSION: The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. CONCLUSION: The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

[Cerebrovascular pharmacology of separate and combined vascular pathology of brain and heart].

The effect of nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA conjugates with arachidonic acid and docosahexaenoyl dopamine on the cerebral circulation has been studied in intact rats and those with global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. The most pronounced vasodilation activity in rats with global transient cerebral ischemia is exhibited by nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA-containing lipid derivatives. This effect of all these drugs (except for nimodipine) is not manifested on the background of GABA receptor blocker bicuculline. In rats with experimental myocardial infarction and combined vascular pathology of brain and heart not all of the compounds mentioned acbove with GABA-ergic mechanism of action stimulate the cerebral blood flow. Thus, both similarity and differences in cerebrovascular effects of these compounds have been found, which depend on the initial state of organism and the vascular pathology of brain and/or heart. The obtained results show good prospects for this direction of research.

[Peculiarities of cerebrovascular effects of GABA conjugate with docosahexaenoyl dopamine under conditions of separate and combined vascular pathology of brain and heart].

A GABA conjugate with docosahexaenoyl dophamine (DHED) enhanced local cerebral blood flow in rats under conditions of global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. At the same time, the GABA-DHED conjugate did not influence brain hemoperfusion in intact animals. The cerebrovascular effect of this conjugate is determined by its direct action on the vascular tone, since no changes in blood pressure have been observed. Under conditions of the combined vascular pathology of brain and heart, the cerebrovascular effect of GABA-DHED conjugate is inhibited by bicuculline, which is evidence for the involvement of GABAergic mechanisms in the drug action upon cerebrovascular tone.

[Cerebrovascular effects of afobazole under conditions of combined disorders of cerebral and coronary circulation].

Influence of afobazole on cerebral blood flow in rats under conditions of global transient ischemia of brain, experimental myocardial infarction, and combined disturbances of coronary and cerebral circulation was studied in comparison to intact and sham operated animals. It is established that afobazole (5 mg/kg) enhances blood flow in parietal region of cerebral cortex of rats after global transient ischemia of brain or experimental myocardial infarction more prominently than in intact and sham operated animals. Moreover, the cerebrovascular effect of afobazole substantially increases under conditions of combined vascular pathology of brain and heart and exceeds its action observed after the cerebral ischemia or myocardial infarction.

[Nimodipine and experimental combined disorders of cerebral and coronary circulation].

The influence of nimodipine on the cerebral circulation of rats under conditions of global transient cerebral ischemia, myocardial ischemia, and combined disorders of cerebral and coronary circulation was experimentally studied in rats, in comparison to the intact and sham operated animals. It is shown that nimodipine (0.03 mg/kg) enhances circulation in the parietal region of the cerebral cortex to the same extent in both intact rats and those after global transient cerebral ischemia. Under conditions of experimental myocardial infarction, the cerebrovascular effect of nimodipine was significantly decreased in comparison to that in intact and sham operated animals. In contrast to intact and sham operated rats and the rats with myocardial infarction, there were no signs of cerebrovascular activity of nimodipine in animals with combined disorders of coronary and cerebral circulation. A new approach to the search for and investigation of pharmacological agents for the treatment of combined disturbances of cerebral and cardiac circulation is proposed.

[Effect of ketamine on cerebral circulation of intact and ischemic animals]. / Vliianie ketamina na mozgovoe krovoobrashchenie intaktnykh i ishemizirovannykh zhivotnykh.

The influence of ketamine on the local cerebral circulation was studied in intact rats and under the conditions of global brain ischemia. The drug increased the local blood flow in intact rats. Despite pronounced hypotension accompanying the global brain ischemia, ketamine helped maintenance of the cerebral circulation.

[Comparative study of dilceren (nimodipine) on the cerebral circulation in the intact animals and animals subjected to ischemic brain damage]. / Sravnitel'noe izuchenie diltserena (nimodipina) na mozgovoe krovoobrashchenie intaktnykh zhivotnykh i posle global'nogo ishemicheskogo porazheniia mozga.

The influence of the calcium entry blocker dilceren (nimodipine) on the local and regional circulation was studied in rats and cats. In the majority of experiments on intact animals, dilceren increased the local and regional blood flow. However, in some cases, the circulation decreased or remained unchanged, which was accompanied by pronounced hypotension. Administered after global brain ischemia, dilceren improved the cerebral hemodynamics in all experiments.

[Effect of dopamineamides of polyunsaturated fatty acids on blood coagulation system and cerebral circulation]. / Vliianie dofaminamidov polinenasyshchennykh zhirnykh kislot na svertyvaiushchuiu sistemu krovi i mozgovoe krovoobrashchenie.

A series of original dopaminamides of polyunsaturated fatty acids were synthesized and characterized with respect to antiaggregant and cerebrovascular stimulant properties. It was established that dopaminamides of linolic, dimethyllinolic, docosapentaenoic, docosahexaenoic (DHEA) and stearidonic (C18:4 and C18:3) acids decrease ADP and arachidonic acid (AA) induced human thrombocyte aggregation in vitro. The most pronounced antiaggregant effect was observed for DHEA dopaminamide: in a dose of 10 mg/kg, this agent produced a significant decrease in the AA induced thrombocyte aggregation. DHEA per se in the same dose increases the activated partial thromboplastin time (APTT), while not affecting the prothrombin time. The synthesized dopaminamides of arachidonic, eicosapentaenoic, and docosahexaenoic acids stimulate local circulation in the cerebral cortex. The most pronounced cerebrovascular effect was also produced by DHEA dopaminamide.