The End Effector of Ischemic Tolerance Present in Blood Plasma from Double Conditioned Donors Ameliorates Trimethyltin Provoked Damage in Brain

Abstract

Background: Hundreds of experiments have been done to demonstrate robust ischemic tolerance efficiency using mostly young and healthy animals. The translation of these results to usually elderly and sick patients moreover taking many various medicines has to date been disappointing. 3-methyltin poisoning, as well as short-term transient cerebral ischemia, causes severe damage, especially to selectively vulnerable brain regions such as hippocampal CA1. Methods: Using dual conditioning, we activated the full ischemic tolerance the products of which is located to blood plasma. As sublethal stresses, two periods of 20-minute hindlimb ischemia was used with a two-day interval between them. Active plasma was isolated 6 hours after the second hindlimb ischemia. Brain damage was detected by visualizing dead neurons by Fluorojade B staining. Neuronal survival by NeuN immunoreaction. The functional capabilities of surviving neurons were monitored by Morris water maze. Results: The use of activated plasma dramatically reduced the hippocampal degenerative CA1 neurons from 56.59% to 7.51%. NeuN positivity increased from 23.82% to 78.67%. Time spent searching for hidden island has been shortened from 48.46 to 21.63 seconds. Conclusions: By using double conditioning it is possible to provoke the synthesis of substances present in the blood plasma, providing the organism with significant protection against acute degenerative processes.