Abstract
Hydrogen sulfide (H2S) is a gasotransmitter endogenously synthesized by cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopiruvate sulfurtransferase (3-MST) enzymes. H2S exogenous administration prevents the development of hemodynamic impairments after traumatic brain injury (TBI). Since the hypothalamus and the brainstem highly regulate the cardiovascular system, this study aimed to evaluate the effect of NaHS subchronic treatment on the changes of H2S-sythesizing enzymes in those brain areas after TBI and in physiological conditions. For that purpose, animals were submitted to a lateral fluid percussion injury, and the changes in CBS, CSE, and 3-MST protein expression were measured by western blot at days 1, 2, 3, 7, and 28 in the vehicle group, and 7 and 28 days after NaHS treatment. After severe TBI induction, we found a decrease in CBS and CSE protein expression in the hypothalamus and brainstem; meanwhile, 3-MST protein expression diminished only in the hypothalamus compared to the Sham group. Remarkably, i.p. daily injections of NaHS, an H2S donor, (3.1 mg/kg) during seven days: (1) restored CBS and CSE but no 3-MST protein expression in the hypothalamus at day 28 post-TBI; (2) reestablished only CSE in brainstem 7 and 28 days after TBI; and (3) did not modify H2S-sythesizing enzymes protein expression in uninjured animals. Mainly, our results show that the NaHS effect on CBS and CSE protein expression is observed in a time- and tissue-dependent manner with no effect on 3-MST expression, which may suggest a potential role of H2S synthesis in hypothalamus and brainstem impairments observed after TBI.
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The data used to support the findings of this study are available from the corresponding author upon request.
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The National Council for Science and Technology (CONACyT) supported this work [Grant No. 252702].
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Huerta de la Cruz S, Rocha L and Centurion D conceived the original idea. Material preparation, data collection and analysis were performed by Huerta de la Cruz S, Rodríguez-Palma EJ, Santiago-Castañeda CL, Beltrán-Ornelas JH and Sánchez-López A. The first draft of the manuscript was written by Huerta de la Cruz S and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Huerta de la Cruz, S., Rodríguez-Palma, E.J., Santiago-Castañeda, C.L. et al. Exogenous hydrogen sulfide restores CSE and CBS but no 3-MST protein expression in the hypothalamus and brainstem after severe traumatic brain injury. Metab Brain Dis 37, 1863–1874 (2022). https://doi.org/10.1007/s11011-022-01033-1
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DOI: https://doi.org/10.1007/s11011-022-01033-1