Ionizing radiation as preconditioning against transient cerebral ischemia in rats

Abstract

Induction of ischemic tolerance (IT), the ability of an organism to survive an otherwise lethal ischemia, is the most effective known approach to preventing postischemic damage. IT can be induced by exposing animals to a broad range of stimuli. In this study we tried to induce IT of brain neurons using ionizing radiation (IR). A preconditioning (pre-C) dose of 10, 20, 30 or 50 Gy of gamma rays was used 2 days before an 8 min ischemia in adult male rats. Ischemia alone caused the degeneration of almost one half of neurons in CA1 region of hippocampus. However, a significant decrease of the number of degenerating neurons was observed after higher doses of radiation (30 and 50 Gy). Moreover, ischemia significantly impaired the spatial memory of rats as tested in Morris's water maze. In rats with a 50 Gy pre-C dose, the latency times were reduced to values close to the control level. Our study is the first to reveal that IR applied in sufficient doses can induce IT and thus allow pyramidal CA1 neurons to survive ischemia. In addition, we show that the beneficial effect of IR pre-C is proportional to the radiation dose.

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

“…The mechanism of its activation includes two steps. The activation initiates the first stress, which may be: 1) projected sublethal stress (preconditioning); 2) pathological situation (ischemia/hypoxia/intoxication), which can be lethal for a group of cells; however, for the rest of the cells it would be a sublethal stress; 3) as a first stress is necessary for the treatment aimed at eliminating an undesirable cell populations what is confirmed by the finding that stressor activating tolerance could also be gamma radiation [24]. Several physical procedures and biological, chemical, or pharmacological compounds can serve as a stressors activating first or, after previous pathological stress, finalizing full tolerance.…”

Cerebral Ischemic Preconditioning: the Road So Far…

“…Metformin, a well-known anti-diabetic drug, has been used to induce PC in rats with promising results, further expanding the scope of PPC [156]. The effects of anti-inflammatory drugs like indomethacin and PC methods like ionizing radiation (IR) have also been newly investigated in the context of CPC [157,158]. Limb preconditioning was seen to be well tolerated in patients with unilateral middle cerebral artery stenosis as well as healthy volunteers [159].…”

An overview of hyperbaric oxygen preconditioning against ischemic stroke

“…Effective preconditioning stimuli vary from transient ischemia, hypoxia, HBO, and low and high temperatures to exposure to neurotoxins and pharmacological agents (Stetler et al 2014 ). Although heavy metals, toxins, ethanol, and ionizing radiation have been successfully used to induce ischemic tolerance in animal models (Fang et al 2020 ; Kokošová et al 2014 ), they are not safe for clinical practice in patients. The goal of developing a safe, practical approach for chemical tolerance seems paradoxical until oxygen is considered.…”