LAUSR

To the Editor: We read with great interest the recent study by Pan et al entitled “MicroRNA-126-3p/-5p Overexpression Attenuates Blood-Brain Barrier Disruption in a Mouse Model of Middle Cerebral Artery Occlusion” published in Stroke. The authors explored the role and potential mechanism of microRNA126-3p/-5p preventing blood-brain barrier (BBB) disruption after ischemic stroke, which suggested microRNA-126-3p/-5p to be a possible treatment target for attenuating BBB dysfunction and improving neurological function after ischemic stroke. We are appreciative of this innovative work; however, we wish to exchange some ideas with the authors. After onset of ischemic stroke, abundant chemokines are released from innate immune cells, which recruit inflammatory cells to secondary damages occurrence. Induced by chemokines like interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), various endothelial adhesion molecules including intercellular adhesion molecule-1, VCAM-1 (vascular cell adhesion molecule-1, P-selectin, and E-selectin were overexpressed. Although the author found that miR-126-3p and -5p could inhibit the expression of VCAM-1 and E-selectin through binding with 3′UTR so that attenuate BBB disruption. Given that the upregulated microRNA-126-3p/-5p also reduced the overexpression of IL-1β and TNF-α after middle cerebral artery occlusion, it cannot be ruled out that the low expression of adhesion molecules was caused by the reduction of inflammatory mediators. Therefore, we suggest the other endothelial adhesion molecules also need to be studied. Furthermore, the activation of adhesion molecules is ultimately related to the inflammatory mediators released by the inflammatory cells they recruit. A more precise BBB protective mechanism of microRNA-126-3p/-5p needs to be further elaborated. Indeed, matrix metalloproteinases have been wildly accepted to damage BBB integrity via degrading tight junctions extracellularly. Tight junctions can also be disrupted via proteasomes and lysosomes after ubiquitination intracellularly. Interestingly, these pathophysiological processes were both accompanied by the infiltration of peripheral immune cells and tightly mediated by inflammatory mediators. These may be the promising targets of microRNA-126-3p/-5p BBB protection as they seem to ultimately reduce recruitment of immune cells and release of inflammatory mediators. Further studies may be needed to clarify these mechanisms for more optimized treatment options.