Hematoencephalic barrier

The most fascinating aspect of the mechanism by which medicinal plants affect the brain function is their ability to elaborate molecules that are able to cross the hematoencephalic barrier and infiltrate the brain where binding to protein receptors occurs. 

Because of their weak lipophily, H-oximes overcome poorly the hematoencephalic barrier. Their antidotic action is based on reactivation of peripheral AChE (in blood and respiratory musculature). 

In the clinical picture of an OPC poisoning, symptoms of CNS impairments (mentality modifications, tremor, periodic clonic/tonic convulsions, etc.) play a leading role. Functional impairments of different CNS parts (encephalon and spinal cord) under influence of OPC are associated with the cerebral ChE activity inhibition and the accumulation of ACh mediator in central synapses. It should be taken into consideration that permeability of the hematoencephalic barrier (HEB) differs in various CNS parts thereby the same substance inhibits ChE in a different degree in various cerebral structures. Along with the factor of selective permeability of various HEB areas and not identical ChE distribution within the brain, one cannot leave out of account selectivity in OPC effects of their own OPC can exhibit higher activity towards a certain cerebral structure. 

Advantages of alloxime over ChR, such as dipiroxime and isonitrosine, consist in more pronounced antidotic-and-therapeutic power at the expense of its ability to penetrate the hematoencephalic barrier and restore activity of cerebral ChE. In addition, it reactivates well activity of blood ChE. The central effect of alloxime is characterized by fast restoration of patients consciousness and improvement in bioelectrical cerebral activity. Its peripheral effects consist in restoration of neuromuscular conduction, normalization of cytochrome P-450 content in the liver and kidneys. Alloxime, similarly to all quaternary oximes of the first generation, is a sufficiently toxic compound. DL50 for the intravenous administration to rats and cats amounts to 135 mg/kg and 126 mg/kg, respectively. 

It seems that this type of oximes may be referred to cholinesterase reactivators of the third generation. This group of compounds lacks the disadvantages inherent to reactivators of the 1st and 2nd generations. Thus, thiohydroxime esters are low toxic and stable in aqueous solutions. Being the substances having a tertiary nitrogen atom in their structure, they penetrate the hematoencephalic barrier and enter CNS readily. 

Thus, the discovered stabilizing efficiency of hybrid antioxidant ichfan on cell membranes with regard to its pronounced antioxidizing effect and feasibility of permeation through the hematoencephalic barrier may be of primary importance for the membrane therapy of neurodegenerative diseases. 

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