An Effective Combination of Two Different Methods of Postconditioning

Abstract

Ischemic tolerance based on the synthesis of protective proteins acquires its full strength by repeated exposure to stress, and "the end effector of tolerance" may paradoxically be activated by the second or lethal stress, particularly in the case of preconditioning. That happens when an additional nonspecific stressor is applied either before (preconditioning) or after (postconditioning) the period of lethal ischemia. A combination of antioxidants with pre or postconditioning prevents the acquisition of tolerance, and in the case of more severe attacks repeated stress can lead to accumulation of damage. Our attempt to weaken ischemic injury to hippocampal CA1 with antioxidants applied after lethal stress, i.e. before delayed postconditioning, was ineffective. We then tried using rapid postconditioning consisting of 30-s reperfusion alternating with 15-s ischemia repeated three times and applied immediately at the end of lethal ischemia as a tool decreasing post-ischemic production of reactive oxygen species, and combining that with delayed postconditioning consisting of an i.p. injection of Bradykinin 2 days after lethal ischemia. This approach once more confirmed the efficacy of both rapid as well as delayed postconditioning but, more importantly, it demonstrated the possibility of effectively combining these two procedures. Our findings further confirm that in cases of delayed neuronal death, which is practically pathologically-induced apoptosis, there exists a 2-day-wide therapeutic window that can be effectively exploited.

Bradykinin Activates the Bradykinin B2 Receptor to Ameliorate Neuronal Injury in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury

“…We found that the bradykinin level was downregulated in blood serum after SCII in rats, and the mRNA and protein expression of B2R both gradually decreased in spinal cord tissues of SCII rats on days 1, 3, 5, and 7 after surgery. Numerous studies have confirmed that bradykinin preconditioning can be effectively used as a stressor inducing ischemic tolerance to protect ischemia injury. − Here, bradykinin and B2R both showed a downward trend, reminding that exogenously administration of bradykinin may have an effect on SCII rats. Then, SCII rats were intraperitoneally injected once a day with 50, 100, and 150 μg/kg bradykinin for 8 days after surgery.…”

Identification of Proteins Responsible for the Neuroprotective Effect of the Secretome Derived from Blood Cells of Remote Ischaemic Conditioned Rats

“…In acute ischaemic stroke, activation of the contact–kinin system fosters vascular permeability and stroke-related inflammation by the formation of short-lived kinins [ 34 ]. On the other hand, bradykinin has been used as a cytoprotective agent against the heart [ 35 ], as well as the brain and spinal cord ischaemia [ 36 , 37 , 38 ]. It is believed that the neuroprotective effect of bradykinin is related to the stress reaction of the organism; its application increases tolerance to ischaemic conditions (pre/postconditioning), so-called ischaemic tolerance.…”

Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia

“…One such strategy is ischemic postconditioning, which may be induced by repeated cycles of transient reperfusion and re-occlusion of the artery, which is applied immediately after reperfusion ( 2 – 4 ). There are two types of ischemic postconditioning: Early and delayed ischemic postconditioning ( 5 ). Rapid postconditioning is induced immediately or a few minutes after reperfusion.…”