Abstract WP246: Intraventricular Administration Of Stanniocalcin-2 Promotes Post-stroke Functional Recovery In A Translational Rodent Model

Abstract

Enhancing an endogenous stem cell response is a promising approach to improve stroke recovery. We have previously shown that a conductive polymer cannula system for human stem cell delivery and electrical stimulation of the post-stroke environment increases endogenous stem cell production and improves functional recovery in a rodent model of distal middle cerebral artery occlusion (dMCAO). Transcriptomic analyses coupled with lentiviral manipulation identified stanniocalcin 2 (STC-2) as one key mediator of this functional improvement. To further investigate the role of STC-2, we intraventricularly administered recombinant STC-2 one week post-dMCAO and assessed functional recovery via vibrissae-forepaw (WP) test at 5 weeks. Our results indicate that intraventricular injection of STC-2 alone post-stroke improves functional recovery in comparison to a control and intraventricular saline group (n=10 per group, p=<0.001, see Figure 1A). Histological analyses revealed an increase in endogenous stem cells that express immature neuronal markers (doublecortin, colocalized with bromodeoxyuridine) between the subventricular zone and peri-infarct region of the STC2-treated group (n=5 per group; p=0.019, see Figure 1B). Additional studies are necessary in order to further elucidate the causative molecular mechanisms involved; however, we believe this study yields great translational potential as our results may help enable a route to augment endogenous responses in the post-stroke environment.