Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke

Escobar-Peso A, Martínez-Alonso E, Masjuan J, Alcázar A. Antioxidants (Basel). 2023 Dec 12;12(12):2102. doi: 10.3390/antiox12122102. PMID: 38136221

Abstract: Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented as a need. With this goal in mind, our research group’s collaborative studies into cerebral ischemia and subsequent reperfusion concluded that there is a need to develop compoundswith antioxidant and radical  scavenger features. In this review, we summarize the path taken toward the identification of lead compounds as potential candidates for the treatment of acute ischemic stroke. Evaluations of the antioxidant capacity, neuroprotection of primary neuronal cultures and in vivo experimental models of cerebral ischemia, including neurological deficit score assessments, are conducted to characterize the biological efficacy of the various neuroprotective compounds developed. Moreover, the initial results in preclinical development, including dose–response studies, the therapeutic window, the long-term neuroprotective effect and in vivo antioxidant evaluation, are reported. The results prompt these c mpounds for clinical trials and are encouraging regarding new drug developments aimed at a successful therapy for ischemic stroke.

Funding: This work was funded by Instituto de Salud Carlos III through the projects PI22/01381 and RICORS RD21/0006/0019 and co-funded by the European Union. A.E.-P. and E.M.-A. thank the Instituto de Salud Carlos III for the contracts IFI18/00011 and RD21/0006/0019, respectively, co-funded by the European Union.