Role of peroxisome proliferator‐activated receptors in stroke prevention and therapy—The best is yet to come?

Abstract

Role of peroxisome proliferator-activated receptors (PPARs) in the pathophysiology of stroke and protective effects of PPAR ligands have been widely investigated in the last 20 years. Activation of all three PPAR isoforms, but especially PPAR-γ, was documented to limit postischemic injury in the numerous in vivo, as well as in in vitro studies. PPARs have been demonstrated to act on multiple mechanisms and were shown to activate multiple protective pathways related to inflammation, apoptosis, BBB protection, neurogenesis, and oxidative stress. The aim of this review was to summarize two decades of PPAR research in stroke with emphasis on in vivo animal studies. We focus on each PPAR receptor separately and detail their implication in stroke. This review also discusses recent clinical efforts in the field and the epidemiological data with regard to role of PPAR polymorphisms in susceptibility to stroke, and tries to draw conclusions and describe future perspectives.

Neuroprotective and antioxidative effects of pioglitazone in brain tissue adjacent to the ischemic core are mediated by PI3K/Akt and Nrf2/ARE pathways

“…The data substantiates the relevance of cerebral PPARγ for protection of neurons against ischemic damage which at last results in the improved recovery from cerebral ischemia. The results provide novel insight into the neuroprotective mechanisms linked to the activation of cerebral PPARγ and the rationale for conducting additional clinical trials investigating the use of pioglitazone in acute treatment of patients suffering from ischemic stroke [ 30 ].…”

Microglial/Macrophage polarization and function in brain injury and repair after stroke

“…Vx‐765, a small‐molecule caspase‐1 inhibitor, mediates M2 microglia/macrophage polarization by suppressing NF‐κB activation 79 . As mentioned previously, widely used PPARγ agonists such as pioglitazone and rosiglitazone can propel microglia toward anti‐inflammatory phenotypes 81 . The repurposing of these drugs may pave a new avenue for stroke treatment.…”

Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke

“…As for Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear transcription factor widely expressed in macrophages and microglia (Li L. et al, 2021). Moreover, it is considered to be an effective therapeutic target for cerebral ischemia (Villapol, 2018;Gamdzyk et al, 2020;Li L. et al, 2021). In addition to its recognized anti-inflammatory effect, it can also reduce oxidative stress, BBB injury, apoptosis, and promote angiogenesis and neurogenesis (Ballesteros et al, 2014; Villapol, 2018;Gamdzyk et al, 2020).…”

“…Moreover, it is considered to be an effective therapeutic target for cerebral ischemia (Villapol, 2018;Gamdzyk et al, 2020;Li L. et al, 2021). In addition to its recognized anti-inflammatory effect, it can also reduce oxidative stress, BBB injury, apoptosis, and promote angiogenesis and neurogenesis (Ballesteros et al, 2014; Villapol, 2018;Gamdzyk et al, 2020). To explore whether SAC passes PPARγ-mediated pathway to promote the recovery of cerebral ischemic injury, some rats with MCAO were treated with SAC and then the protein expression of PPARγ was verified.…”