Calmodulin in Brain Tissues of Newborn Rats with Hypoxic-Ischemic Encephalopathy and the Therapeutic Effect of Cerebrolysin

Objective To study the relationship between calmodulin (CaM) concentrations in brain tissues of newborn rats and the pathogenesis of hypoxic ischemic encephalopathy (HIE) and the therapeutic effect of cerebrolysin on HIE. Methods Morphological and metabolic effects of cerebral ischemia were investigated in a newborn rat model of neonatal HIE. In addition, the effect of cerebrolysin (EBEWE, Austria) on acute brain hypoxic ischemia was studied. Eighty eight HIE newborn rats (48 cerebrolysin treated and 40 controls) were subjected to left cerebral artery ligation and one hour later they were placed in a hypoxic environment (8% oxygen and 92% nitrogen mixed) for two hours. Immediately afterwards, cerebrolysin ( 2.5 ml/kg body mass) was administered daily, either by intracerebroventricular infusion (i.c.v) or by intramuscular injection. CaM concentrations were determined using cyclicnucleotide dependent phosphodiesterase methods, and 15 normal rats were used as the control group. Results CaM concentrations in brain tissues increased in HIE group at different duration after hypoxic ischemia: 24 h=( 521.27 ± 46.04 ) μg/g brain tissue; 48 h=( 509.52 ± 35.98 ) μg/g brain tissue; 72 h=( 421.05 ± 31.81 ) μg/g brain tissue, compared to the control group [( 187.63 ± 54.22 ) μg/g brain tissue] (P 0.01 ). Cerebrolysin treatment groups facilitated recovery, as indicated by a decrease in CaM concentration (i.c.v group: 24 h=( 435.21 ± 56.17 ) μg/g brain tissue; 48 h=( 260.38 ± 32.43 ) μg/g brain tissue; 72 h=( 197.64 ± 19.21 ) μg/g brain tissue; i.m.group: 24 h=( 441.04 ± 30.66 ) μg/g brain tissue; 48 h=( 305.39 ± 32.99 ) μg/g brain tissue; 72 h=( 217.71 ± 52.89 ) μg/g brain tissue (P0.01). Morphological examination showed that the volume of neuron degeneration, necrosis and intercellular edema was increased in HIE groups and significantly reduced in cerebrolysin treatment groups. Conclusions CaM concentration in brain tissues is increased after hypoxic ischemic injury and may be implicated in the pathogenesis of newborn rats with HIE. Cerebrolysin is effective in protecting brain cells from further damage through its influence on cerebral CaM concentration.