Targets of rational neuroprotection in the therapy of chronic cerebral ischemia and the possibilities of achieving them

Chronic cerebral ischemia (CCI) remains one of the leading causes of cognitive and neurological impairments that reduce the quality of life and work capacity of patients. Despite extensive research and development of pharmacology, effective neuroprotective approaches are still limited. The article reviews the key pathogenetic mechanisms of CCI: microcirculatory disorders, glutamate-mediated excitotoxicity, oxidative stress and neuroinflammation. The authors emphasize the need for target-oriented therapy capable of influencing various links of the ischemic cascade. Special attention is paid to the role of Cortexin, a peptide drug with proven neuroprotective effect. Its molecular mechanisms are discussed: normalization of glutamatergic transmission, antioxidant and anti-inflammatory action, restoration of blood-brain barrier. The results of experimental and clinical studies demonstrating the effectiveness of Cortexin in conditions of ischemic brain damage are presented. Biomarkers confirming the effect of Cortexin on the reduction of neurotoxicity (in particular, NR2-peptide concentration), enhancement of antioxidant activity and modulation of cytokine profile are analyzed separately. The article emphasizes the need to revise traditional concepts of neuroprotection in favor of pathogenesis-oriented, multitarget approaches. Cortexin is presented as a promising drug that meets modern requirements for rational neuroprotection in chronic cerebral ischemia.