Promoting brain remodeling to aid in stroke recovery

Abstract

Endogenous brain repair after stroke involves a set of highly interactive processes, such as angiogenesis, neurogenesis, oligodendrogenesis, synaptogenesis and axonal outgrowth, which together orchestrate neurological recovery. During the past several years, there have been advances in our understanding of miRNAs and histone deacetylases (HDACs) in brain repair processes after stroke. Emerging data indicate the important role of exosomes for intercellular communication in promoting coupled brain remodeling processes. These advances will likely have a major impact on development of restorative therapies for ischemic brain repair, consequently leading to improvement of neurological function. In this review, we provide an update on our current understanding of cellular and molecular mechanisms of miRNAs, exosomes, and HDACs in brain restorative processes after stroke.

Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury

“…Exosomes, depending on their parental origin, contain a variety of proteins, lipids, noncoding RNAs, mRNA, and miRNA, collectively termed as “cargo” contents (Kalani et al, 2014). Contained among these constituents, miRNAs may play a key role in mediating biological function due to their prominent role in gene regulation, as we demonstrate that MSCs communicate with brain parenchymal cells and regulate neurite outgrowth by transfer of miR-133b to neural cells via exosomes (Xin et al, 2012; Xin et al, 2014; Xin et al, 2013c; Zhang and Chopp, 2015, 2016). In addition, we performed the control treatment with the artificial exosome membrane, which consists of the same lipid content as exosomes but lacks content of proteins and genetic materials.…”

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

“…That the brain remodels itself after stroke has been documented (Hermann et al, 2014; Tajiri et al, 2012; Watson et al, 2015; Zhang & Chopp, 2015), but this host repair mechanism is not sufficient to account for sustained relevant stroke recovery (Doeppner et al, 2009; Hess & Borlongan, 2008a; Hu et al, 2013; Kuge et al, 2009). Exogenous treatment, either pharmacologically or via stem cell transplantation, designed to enhance host brain regenerative process is needed to achieve clinically relevant functional outcomes in stroke (Kaneko et al, 2012; Matsukawa et al, 2009; Peña & Borlongan, 2015; Tajiri et al, 2012; Wang et al, 2014; Yasuhara et al, 2010).…”

Exosomes in stroke pathogenesis and therapy

“…Exosomes transfer their cargo miRNAs to recipient cells (120,121) and MSC-derived exosomes contain more than 700 miRNAs that are bound to argonaute2 (AGO2), a component of the RNAinduced silencing complex (RISC) (122,123). The effect of engineered MSC-derived exosomes that carry elevated miRNAs on brain remodeling after stroke has been investigated in vitro and in vivo (118,119).…”