Abstract
Purulent meningitis (PM) is a severe disease, characterized by high mortality and a formation of a residual neurological deficit. Loss of treatment of PM leads to the lethal outcome in 100% of cases. In addition, death and the development of residual neurological complications are possible despite adequate therapy. The aim of the study was to evaluate the cerebroprotective effects of a new pharmacological compound 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid (EMHDPA) on the bacterial purulent meningitis in a model of experimental pneumococcal meningitis. Meningitis was simulated by intrathecal injection of the suspension containing Streptococcus pneumoniae at the concentration of 5 × 109 CFU/mL. The cerebroprotective effect was evaluated by survival rates, the severity of neurological deficit, investigatory behaviors, and results of short-term and long-term memory tests. The group administered with EMHDPA showed high survival rates, 80%. Animals treated with the studied compound showed a higher clinical assessment of the rat health status and specific force, and a lesser intensity of neurological deficit compared to the control group (p < 0.05). Locomotor activity of the animals treated with EMHDPA was significantly higher compared to the control group (p < 0.05). There is a decrease in the activity of all estimated indicators of oxidative stress in the group administered with 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid relative to the control group: a decrease in the activity of catalase—17%, superoxide dismutase—34%, malondialdehyde and acetylhydroperoxides—50%, and nitric oxide—85% (p < 0.05). Analysis of the data obtained during the experiment leads to the conclusion about the effectiveness of 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid in the treatment of the experimental PM.
Highlights
The group administered with EMHDPA had the highest survival rate, 80%
On the first and third days after meningitis simulation, the rats treated with EMHDPA had a better clinical assessment of their health by 36.7% and 20.8%, respectively, statistically significant compared to the control group (p < 0.05)
The severity of neurological deficit in the group administered with EMHDPA, on the first, fifth and eighth day after pathology simulation, was statistically significantly less pronounced compared to the control group by 10.2%, 12%, and 14.2%, respectively (p < 0.05)
Summary
Purulent meningitis (PM) is usually a severe disease characterized by high mortality and the formation of a residual neurological deficit after the disease. Loss of treatment of PM leads to the lethal outcome in 100% of cases. Death and the development of residual neurological complications are possible despite adequate therapy. The incidence of bacterial meningitis is about five cases per 100,000 adults per year in developed countries and can be 10 times higher in less developed countries. The predominant pathogens in adults are Streptococcus pneumoniae (pneumococcus) and Neisseria
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