Exosome-mediated amplification of endogenous brain repair mechanisms and brain and systemic organ interaction in modulating neurological outcome after stroke

Abstract

Ischemic stroke is caused by a regional interruption of cerebral blood flow to the brain. Rigorous pre-clinical and clinical research has made landmark progress in stroke treatment using thrombolytics and endovascular thrombectomy. Although numerous successful neuroprotective therapeutic agents for ischemic stroke have been reported in pre-clinical studies, most of them failed in clinical testing. Persistent pre-clinical research has demonstrated that the ischemic brain is not only passively dying but is also actively recovering. Within the neurovascular niche in the peri-infarct tissue, repair mechanisms thrive on the interactions between the neural and vascular compartments. In this review, we discuss exogenous therapy using mesenchymal stromal cell-derived exosomes to amplify endogenous brain repair mechanisms and to induce neurorestorative effects after stroke. Emerging evidence indicates that multiple communication axes between the various organs such as the brain, heart, kidney and gut, and whole body immune response mediated by the spleen can also affect stroke outcome. Therefore, in this review, we summarize this evidence and initiate a discussion on the potential to improve stroke outcome by amplifying multiple brain repair mechanisms after stroke, and by targeting peripheral organs and downstream events to enhance recovery in the injured brain and promote over all well being.

Keywords: Exosome; microRNA; neurorestoration; neurovascular niche; stroke.

Figure 1.

Summary of MSC-exosome-derived therapeutic effects after stroke. MSC-derived exosomes transfer microRNA to the various cells of the neurovascular unit as well as stimulate parenchymal brain cells to secrete growth and trophic factors which promote neurorestorative mechanisms such as angiogenesis, neurogenesis, synaptogenesis, oligodendrogenesis, and anti-inflammatory responses which contribute to neurological functional recovery after stroke.

Figure 2.

Summary of stroke-induced peripheral organ injury. Stroke induces systemic inflammation and activates peripheral immune response which aggaravates ischemic brain injury as well as contributes to stroke-induced peripheral organ injury such as gut dysbiosis, cardiac dysfunction and renal disease.