Post-stroke Impairment of the Blood –Brain Barrier and Perifocal Vasogenic Edema Is Alleviated by Endovascular Mesenchymal Stem Cell Administration: Modulation of the PKCδ/MMP9/AQP4-Mediated Pathway

AbstractPost-stroke edema and upregulation of aquaporin 4 (AQP4) water transport channels play a significant role in the progression of stroke pathology and deteriorating stroke outcomes. Prior studies from our lab have demonstrated the safety and efficacy of intra-arterial (IA) 1  × 105 mesenchymal stem cells (MSCs) administration post-stroke towards functional restoration and neuroprotection. Protein kinases have been reported to be involved in the signaling cascade of edema, with evidence supporting both its upregulation and downregulation at 24  h post-stroke. Among different protein kinase C (PKC) isoforms, the δ isoform is widely reported to play a pivotal role in the progression of ischemic reperfusion injury. Our present study aims to decipher the molecular mechanism of post-stroke IA MSCs mediated alleviation of perifocal vasogenic edema by PKCδ-mediated AQP4 regulation. Ovariectomized female SD rats were infused with 1 × 105 IA MSCs at 6  h post middle cerebral artery occlusion (MCAo). Animals were evaluated for behavioral and functional outcomes. Brains were harvested for evaluating infarct size and brain edema. Further, brain tissues were used for biochemical and molecular studies to decipher the possible molecular mechanism rela ted to the regulation of PKCδ-mediated AQP4 expression. 1 × 105 IA MSCs at 6  h post-stroke confers neuroprotection as evident by the reduction in infarct size, edema, and improvement of functional outcome. An increas...
Source: Molecular Neurobiology - Category: Neurology Source Type: research