Merabolomicschanges Of Brain Stem Respiratory Center(PreBotC) In Severe TBI And The Relationship With Respiratory Function

Traumatic brain injury, With the development of social economy, cause millions of deaths and disability annually, has been a major threat to human health problems.lt is the major cause of death in severe traumatic brain injury that brainstem respiratory dysfunction could not get the exact treatment. As the respiratory rhythm pacemaker, pre-Botzinger complex provides the anatomical basis in order to further reveal the brainstem respiratory function. Metabolomics is a systems biology approach of small molecule metabolites, compared with proteomics,more emphasis on disease pathological changes in real-time table-type, showing the process of dynamic change.By the application of the metabonomics approach-HNMR technology, we used brain stem respiratory center preBotC after severe traumatic brain injury in rats as the research object to phylogeneticly study preBotC metabolic changes in severe head injury rat from phylogeneticly, and analysis the comparative metabolism to explore small molecules respiratory-related for further treatment.I Establishment of the severe head injury model with respiratory insufficiency in rats and the positioning of the brain stem respiratory center (PreBotC).Objective:To research the establishment of the severe head injury model with respiratory insufficiency in rats, and the positioning of the brain stem respiratory center (PreBotC). Above researches provided model foundation for the severe traumatic brain injury with respiratory insufficiency and methodological basis for the brainstem respiratory center (PreBotC) in further studies.Methods:Using of hydraulic injury equipment in male SD rats(impact force,2.7-2.8atm), we prepared severe traumatic brain injury model with respiratory dysfunction(experimental group), according to blood gas analysis in 2h after injury. At the same time, we made precise positioning of preBotC through its specific NK-1 immunohistochemical stainingin the anatomical plane of the hypoglossal nerve location.Results:After injury, there was the brain stem inhibition of the slow breathing, low blood pressure and heart rate, of which the most significant changes in respiration. Also there showed a brief apnea with the duration of 1-10 minutes immediately after injury. With the animal ventilator-assisted breathing, the 80.0% (36/40) in rats can restore breathing irregular breathing on their owns, and eventually there were 33 animals belongs to severe traumatic brain injury with respiratory insufficiency group by blood gas analysis standards (referred to as'experimental group').Conclusion:Successful establishment of the severe head injury model with respiratory insufficiency in rat,which was with of good stability, good reproducibility and good survive for more than 2 hours through timely and effective aid. Complements of anatomical location and histological preparation about preBotC:By the anatomical location of hypoglossal nerve, NK-1 immunohistochemistry could precise position preBotC, so we prepared successfully is the preBotC tissue section included in the hypoglossal nerve.II Comparative metabonomic studies in preBotC of severe brain injury rats-1HNMRObjective:To investigate method of setting up comparative metabonomics of rats preBotC after severe TBI,and establish corresponding comparative metabonomics, Above researches provided research base for relationship between respiratory function and comparative metabonomics of rats preBotC after severe TBI.Methods:To make metabolic research on PreBotC tissues through NMR spectroscopy, the data obtained were analyzed with statistical software. Results:Through the analysis of the HNMR metabolomics technical, we can get 10 comparative metabolites of preBotC in rats after severe traumatic brain injury,7 of which were significantly higher like glycine, y-aminobutyric acid, taurine, lactate, creatine, creatine phosphate,aspartate and other amino acids, and 3 of which were significantly reduced such as isoleucine. These are mainly involved in brain energy metabolism, oxidative damage, inhibition and excitatory central nervous system changes.Conclusion:Through analyzing the comparative metabonomics of brain stem respiratory center (preBotC) after severe traumatic brain injury,we found that relative concentration of glycine, y-aminobutyric acid, taurine, lactate, creatine, creatine phosphate, aspartic acid is increased Relative concentration of isoleucine is decreased.These changes may be related to trauma,stability and reproducibility of Proton magnetic resonance spectroscopy are good; It required a little tissue, which is more suitable for study of the respiratory center and the hypothalamus and other Crucial neural nuclei;It is closest to the original state because of less operation of the sample.â…¢,Comparative metabonomics in preBotC of severe brain injury rats and its relationship with respiratory function.Objective:To investigate relationship between changes of respiratory function and comparative metabonomics of rats preBotC after severe TBI, To establish the comparative respiratory-related metabonomics in preBotC.The functional analysis of comparative metabonomics in preBotC of severe brain injury rats could provide possible new targets for the treatment.Methods:To make preBotC metabolic research trough NMR spectroscopy for severe TBI with respiratory insufficiency,and to the analysis spectral data by the statistical software.Results:Through the analysis of the HNMR metabolomics technical, there were a total of 8 respiratory rhythm-related comparative metabolites of preBotC after severe traumatic brain injury, compared with the accelerated respiration group,the group respiratory frequency decreased were significantly higher like lactate, creatine,phosphate creatine, aspartate, N-acetyl-aspartic acid, and were significantly reduced such as leucine, valine, isoleucine.Conclusion:combined with respiratory changes, we found that relative concentration of lactate, creatine, creatine phosphate, aspartate, N-acetyl-aspartate were increased, leucine, valine, isoleucine were decreased. These changes may be related to slow down of breathing. The concentration changes of these metabolites may be related to slowed down of respiratory frequency after trauma.