Abstract WP99: Post-stroke PPARγ Activation Promotes The Proliferation And Differentiation Of Innate- And Bone Marrow-derived Stem Cells In Subventicular Zone, Leading To Vasogenesis And Neurogenesis In Cortex

• DOI: 10.1161/str.44.suppl_1.awp99
• Publication Date: 2022-03-20T05:12:15Z
• Authors: Tomoya Kinouchi; Yoshitaka Kurashiki; Keiko T Kitazato; Kenji Shimada; Kenji Yagi; Yoshiteru Tada; Nobuhisa Matsushita; Manabu Sumiyoshi; Junichiro Satomi; Masataka Sata; Shinji Nagahiro
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Background and Purpose— Neuroprotection after ischemia by pretreatment with a peroxisome proliferator-activated receptor gamma (PPARγ) agonist was associated with the transcriptional activation of anti-apoptotic- and survival genes via p-STAT3 in oophorectomized (OVX) rats. Based on this finding, we hypothesized that post-stroke PPARγ activation contributes to neurogenesis.

Methods— To examine the proliferation and differentiation after cerebral ischemia of innate- and bone marrow (BM)-derived stem cells, we treated 13 week-old OVX Wistar rats with the PPARγ agonist. After replacing their BM cells with BM cells from green fluorescent protein transgenic (GFP) rats they were subjected to 90-min cerebral ischemia and divided into 2 groups. One was treated with pioglitazone (PGZ, 2.5 mg/kg/day) for 14 days after ischemia induction. The other was vehicle-control (VC).

Results— Compared to VC, neurological deficits and infarct volumes were significantly reduced in rats treated with PGZ. In the VC rats innate- and BM-derived stem cells in the subventricular zone (SVZ) were slightly increased after ischemia. Notably, in the PGZ group, the proliferation of both cell types was evidently augmented with PPARγ expression. They were translocated from the SVZ into the cortical peri-infarct area. There they differentiated into neurons, glia, and blood vessels and the expression of phosphorylated Akt, VEGF, and of BrdU incorporated into the cells was increased. This suggested the PGZ-induced vasogenesis and neurogenesis via activation of cell survival- and proliferation signals, resulting in the neurological improvement and the reduction of infarct size.

Conclusions— Our findings provide new evidence in OVX rats that PPARγ activation after ischemia promotes the proliferation and differentiation of innate- and BM stem cells, leading to good outcome.