Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke

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 compounds with 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 compounds for clinical trials and are encouraging regarding new drug developments aimed at a successful therapy for ischemic stroke.

The Effect and Mechanism of Oleanolic Acid in the Treatment of Metabolic Syndrome and Related Cardiovascular Diseases

“…The key mechanism in the formation of ischemic stroke is oxidative stress [ 112 ], which also causes neuronal apoptosis, inflammation, and nerve injury [ 113 ]. It was reported that OA reduced cerebral ischemic stroke damage by increasing the level of mitochondrial antioxidant α-tocopherol (α-TOC) and GSH, as well as decreasing the leakage of the damage marker lactate dehydrogenase (LDH) [ 114 ].…”