**5. Conclusions**

Methods of preventive gene therapy of ischemic stroke in at-risk patients are currently unknown. In this study, for the first time, we provide evidence of the beneficial effects of preventive triple gene therapy by an adenoviral- or UCB-MC-mediated intrathecal simultaneous delivery combination of *vegf165*, *gdnf*, and *ncam1* on the preservation and recovery of the brain in rats with subsequent modelling of stroke. The obtained data represent a novel and potentially successful approach for ischemic stroke treatment in patients.

**Author Contributions:** Conceptualization, R.I.; Data curation, V.M. and M.K.; Formal analysis, M.K.; Investigation, V.M., F.F., M.S., D.T., E.K., G.K., A.G. and I.S.; Methodology, Z.S., A.I. and F.F.; Project administration, V.M., Z.S., A.I., F.F. and M.S.; Supervision, F.B. and R.I.; Visualization, A.I. and L.N.; Writing—original draft and review & editing, R.I. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the grant of Russian Science Foundation No. 19-75-10030.

**Acknowledgments:** Some experiments were carried out as part of the state assignment of the Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences".

**Conflicts of Interest:** The authors declare no conflict of interest.
