Postconditioning-induced neuroprotection, mechanisms and applications in cerebral ischemia

- PostC can be induced by sublethal ischemia, remote ischemia, or chemical treatments.
- PostC has multi-mechanism that act at almost every aspect of ischemic stroke injury.
- A few issues should be resolved, such as the time window, risks, efficiency, and impacts of risk factors for stroke and t-PA.

Ischemic postconditioning (PostC) is defined as a series of rapid intermittent interruptions of blood flow at the phase of reperfusion, which produces neuroprotection against cerebral ischemia/reperfusion injury via mobilizing the brain's own endogenous adaptive mechanisms. Now the concept of conventional ischemic PostC has been extended to limb remote ischemic PostC and chemical PostC with hypoxia, volatile anesthetic, CO2, etc. According to the different temporal profile of PostC, it is divided into rapid and delayed PostC. Rapid PostC is applied within a few seconds to minutes after reperfusion, while delayed PostC is applied at a few hours to days after reperfusion. Although the neuroprotective mechanisms of PostC are not completely elucidated, a series of mechanisms have been found to connect with PostC in the central nervous system, such as regulating synaptic signaling, attenuating oxidative stress and inflammation, maintaining mitochondrial integrity, inhibiting endoplasmic reticulum stress, regulating autophagy, activating PI3K/Akt pathway, inhibiting apoptosis, protecting neurovascular unit, etc. Based on these multiple protective mechanisms, PostC has high expectations to translate to the clinic, but a few issues should be resolved such as the time window, risks, efficiency, the impact of age, gender, hypertension, hyperlipidemia and t-PA, and clinical maneuverability. Even so, PostC could soon be at the bedside if the clinical trials are carefully planned.