Prospects of pharmacological regulation of physiological adaptation mechanisms in cerebrovascular insufficiency

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Abstract

In cerebrovascular insufficiency, neuroprotective pharmacotherapy is usually carried out in 2 strategic directions: blockade of pathophysiological reactions of ischemic cascades and increase in the tolerance of brain neurons to ischemia/hypoxia. This approach to pharmacotherapy of patients with ischemic brain damage is the key to effective neuroprotection. Pharmacological blockade of ischemia-induced pathophysiological reactions is achieved by using drugs that affect pathogenetic targets in the dynamics of the ischemic process, which allows blocking the development of neurotoxic effects and reducing the likelihood of functional and structural changes in neurons. The work discusses the prospects for pharmacotherapy of cerebrovascular insufficiency through activation of endogenous adaptation mechanisms. The author’s own research and other sources data on the efficacy and safety of various pharmacotherapeutic agents are analyzed. The neuroprotective effects of these agents are based on activating physiological mechanisms of cellular adaptation to ischemia/hypoxia. A pharmacotherapeutic rationale is given for selecting and evaluating the pharmacodynamics of agents aimed at stimulating physiological mechanisms of neuroprotection (including neurotrophic and neuroplasticity processes). Neuroprotective pharmacotherapy for both acute cerebrovascular accidents and chronic cerebrovascular insufficiency should be combined and aimed not only at blocking pathological reactions of the ischemic cascade but also at activating endogenous adaptation mechanisms. The selection of pharmacological agents for implementing pharmacological neuroprotection by activating physiological adaptation mechanisms depends on the neuroprotection period and the intended pharmacological targets.

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About the authors

Vasiliy E. Novikov

Smolensk State Medical University

Author for correspondence.
Email: farmfpk@smolgmu.ru
ORCID iD: 0000-0002-0953-7993
SPIN-code: 1685-1028

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Smolensk

Elena V. Pozhilova

Smolensk State Medical University

Email: elena-pozh2008@yandex.ru
ORCID iD: 0000-0002-7372-7329
SPIN-code: 6371-6930

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Smolensk

Natalia E. Usacheva

Smolensk State Medical University

Email: farmfpk@smolgmu.ru
ORCID iD: 0000-0002-4416-4344
SPIN-code: 1512-1336

Cand. Sci. (Pharmacology), Assistant Professor

Russian Federation, Smolensk

Ksenia D. Zagnet

Smolensk State Medical University

Email: farmfpk@smolgmu.ru
ORCID iD: 0000-0003-0761-7129
SPIN-code: 9179-0791

Assistant

Russian Federation, Smolensk

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2. Fig. 1. The effect of amthysole and moderate hypobaric hypoxia (HBH) on neurological deficit (assessed using the McGraw scale) in rats 1 day after bilateral common carotid artery occlusion. Differences are considered significant at p <0.05 (Mann–Whitney U test) compared with the following groups: * — sham-operated group, # — “Ischemia” group

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