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

Abstract

Background: Many experiments have been done to demonstrate robust ischemic tolerance efficiency using mostly young and healthy animals. However, the translation of these results to usually elderly and sick patients moreover taking many various medicines has to date been disappointing. 3-Methyltin (TMT) poisoning and short-term transient cerebral ischemia cause similar damage, especially, to selectively vulnerable brain regions such as hippocampal CA1 and CA3. Methods: Using dual conditioning, we activated the full ischemic tolerance the products of which are located to blood plas ma. As s ublethal stresses, two periods of 20-minute hind-limb ischemia was used with a two-day interval in rats. Active plas ma was isolated 6 h after the second hind limb ischemia. Brain damage was detected by visualizing dead neurons by Fluoro-Jade B s taining and neuronal s urvival by NeuN immunoreaction. The functional capabilities of the surviving neurons were monitored by the Morris water maze.

Ischemic Tolerance—A Way to Reduce the Extent of Ischemia–Reperfusion Damage

“…Based on several works [ 36 , 97 ], it can be concluded that the end effector of ischemic tolerance passes through the blood–brain barrier, meaning that its application will not be limited to only one organ, and its action will be possible immediately in the whole organism. These assumptions were also confirmed by our results [ 96 , 97 ], where we clearly demonstrated the unequivocal effect of activated plasma on the survival of skeletal muscle cells as well as brain cells in the CA1 hippocampus.…”

“…Based on other works, it can be assumed that interleukins, stromal factor+-α, TNF-α, bradykinin-2, adenosine, opioids, NO, miRNA, and possibly catecholamines can be possible triggers of tolerance [ 95 ]. The assumption of humoral transfer clearly supports the transfer of ischemic tolerance with blood plasma from a 2× conditioned donor [ 96 , 97 ].…”