The protective effect of DMI on hippocampus EEG, behavioral and biochemical parameters in hypoxia-induced seizure on neonatal period

Abstract

Hypoxia-Induced Neonatal Seizure (HINS) is a prevalent type of seizure in infants caused by hypoxic conditions, which can lead to an increased risk of epilepsy, learning disabilities, and cognitive impairments later in life. This study focuses on examining the effects of dimethyl itaconate (DMI) on cognition, motor coordination, and anxiety-like behavior in male rats that have experienced HINS. 42 male Wistar newborn rats (PND10) were randomly divided into six groups (n = 7). 1) Control (Vehicle only); received DMI solvent (0.1ml) without applying hypoxia. 2–3) DMI; receiving (20 and 50 mg/kg; i.p). 4) HINS; they were placed in a hypoxia chamber with 7% oxygen and 93% nitrogen concentration for 15 minutes. 5–6) DMI+HINS; received DMI (20 and 50 mg/kg; i.p) 24h before hypoxia. Behavioral tests including; Novel object recognition test, Rotarod, Parallel bar, Open field and elevated plus maze (EPM); started at age 45 after birth. After behavioral tests, the hippocampal CA1 region local EEG was recorded in all groups. Then the brain hippocampus tissue was isolated and the amount of MDA, SOD, NO, and Thiol was measured by ELISA method. Data showed that the administration of DMI improved motor symptoms, anxiety-like behaviors, and cognition in HINS rats (p<0.05). EEG power in the HINS group decreased significantly compared to other experimental groups (p<0.05). Biochemical observations showed that DMI significantly reduced oxidative stress and inflammation in the hippocampal tissue of HINS rats (p<0.05). Increased hippocampal oxidative stress and inflammation can be effective in the occurrence of behavioral disorders observed in HINS rats. While DMI improved these behavioral impairments by reducing oxidative stress and inflammation.