@misc{10481/97465,
year = {2024},
month = {11},
url = {https://hdl.handle.net/10481/97465},
abstract = {Ischemic stroke is the result of a permanent or transient occlusion of a brain artery, leading to irreversible tissue
injury and long-term sequelae. Despite ongoing advancements in revascularization techniques, stroke remains
the second leading cause of death worldwide. A comprehensive understanding of the complex and interconnected
mechanisms, along with the endogenous mediators that modulate stroke responses is essential for the
development of effective interventions. Our study investigates cortistatin, a neuropeptide extensively distributed
in the immune and central nervous systems, known for its immunomodulatory properties. With neuroinflammation
and peripheral immune deregulation as key pathological features of brain ischemia, cortistatin
emerges as a promising therapeutic candidate. To this aim, we evaluated its potential effect in a well-established
middle cerebral artery occlusion (MCAO) preclinical stroke model. Our findings indicated that the peripheral
administration of cortistatin at 24 h post-stroke significantly reduced neurological damage and enhanced recovery.
Importantly, cortistatin-induced neuroprotection was multitargeted, as it modulated the glial reactivity
and astrocytic scar formation, facilitated blood-brain barrier recovery, and regulated local and systemic immune
dysfunction. Surprisingly, administration of cortistatin at immediate and early post-stroke time points proved to
be not beneficial and even detrimental. These results emphasize the importance of understanding the spatiotemporal
dynamics of stroke pathology to develop innovative therapeutic strategies with appropriate time
windows. Premature interruption of certain neuroinflammatory processes might inadvertently compromise
neuroprotective mechanisms. In summary, our study highlights cortistatin as a novel pleiotropic therapeutic
approach against ischemic stroke, offering new treatment options for patients who undergo early revascularization
intervention but unsuccessful recovery.},
organization = {Spanish Ministry of Science and Innovation (MCIN)/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”},
organization = {Grants: SAF2017–85602-R and PID2020–119638RB-I00 (to E.G-R.), by the Swiss Science Foundation grant No 310030_212233 and Biaggi Foundation grant (to L.H)},
organization = {FPU-program FPU17/02616 and EMBO-STFL8942 (to J.C-G.)},
organization = {FPI-program PRE2018–084824 (to I.S-M.) and PRE2021–100172 (to P.V-R.)},
publisher = {Elsevier},
keywords = {blood-brain barrier breakdown},
keywords = {cortistatin},
keywords = {ischemic stroke},
title = {Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke},
doi = {10.1016/j.phrs.2024.107501},
author = {Castillo González, Julia and Buscemi, L. and Vargas-Rodríguez, P. and Serrano Martínez, Ignacio and Forte-Lago, Irene and Caro, M. and Price, M. and Hernández Cortés, Pedro Manuel and Hirt, L. and González-Rey, Elena},
}