Pharmacological Modulation of Endogenous Neuroprotection after Experimental Prenatal Hypoxia

Abstract

Abstract—Prenatal hypoxia (PH) causes pathological changes in the brain and can lead to irreversible longterm disorders of brain development and the emergence of neuropsychiatric pathologies in children. Pharmacological correction of post-hypoxic disorders of the central nervous system is a priority in modern medicine. The aim of this work was to study the neuroprotective effects of Angiolin, Thiotriazoline, Tamoxifen, Glutoredoxin, Cerebrocurin, an IL-1b antagonist (RAIL), Mexidol, and L-arginine in comparison with the reference drug Piracetam in terms of their effect on the expression of endogenous neuroprotection factors for further substantiation of their use for treating prenatal CNS lesions in a model of chronic hemic PH. The expression of HSP70, HIF-1, and c-fos mRNAs and the content of HSP70 in the cytoplasmic and mitochondrial fractions of the brain of 60 day old rat pups subjected to PH were studied using real-time PCR and enzyme-linked immunosorbent assay. We found that chronic PH leads to the inhibition of transcriptional processes in neurons and the suppression of HIF1a, HSP70, and c-fos synthesis. The studied drugs modulated the HSP70-mediated mechanisms of endogenous neuroprotection. The most active among HSP70 modulators in chronic PH were Cerebrocurin (150 μL/kg) and Angiolin (50 mg/kg) which surpass the other drugs studied in the level of HSP70 and HIF-1α mRNA expression, as well as HSP70 protein concentration in the brain of experimental animals, and can be viewed as promising neuroprotective agents in complex therapy after PH.