Effects of NaHS and hydroxylamine on the expressions of brain-derived neurotrophic factor and its receptors in rats after cardiac arrest and cardiopulmonary resuscitation.

BACKGROUND: H2 S can also protect nerve cells. The objective of the study is to investigate the effects of hydrogen sulfide (H2 S) on the expressions of brain-derived neurotrophic factor (BDNF) and its receptors, tyrosine protein kinase B (TrkB) and p75 neurotrophin receptor (p75NTR), in brain tissues of rats with cardiac arrest and cardiopulmonary resuscitation (CA/CPR) following the restoration of spontaneous circulation (ROSC).

METHODS: Rats (n = 240) with CA/CPR were divided into three groups: Intervention (n = 80) that received sodium hydrosulfide (NaHS, 14 μmoL/kg·d) intervention after ROSC; Inhibition (n = 80) that received hydroxylamine (40 μmoL/kg·d) intervention after ROSC; and Control (n = 80) that received saline after ROSC. Kaplan-Meyer analysis was used to analyze the survival data. Quantitative real-time PCR (q-PCR), Western blot, immunohistochemistry and IODs (integrated optical density) were performed to determine the mRNA and protein expressions of BDNF, TrkB and p75NTR in rat brain tissues.

RESULTS: Survival rate of the three groups had significant difference (χ2  = 28.376, p = 0.000). The Intervention group had the highest survival rate (82.5%), while the Inhibition group had the lowest survival rate (62.5%). The mRNA and protein levels of BDNF and TrkB in the Intervention group were significantly higher compared to the Control group (p < 0.05); while the mRNA and protein levels of BDNF and TrkB in the Inhibition group was significantly lower than the Control group (p < 0.05) on days 1, 3, and 7. However, the mRNA and protein levels of p75NTR in the Intervention group were significantly lower than the Control group (p < 0.05); while the mRNA and protein levels of p75NTR in the Inhibition group were significantly higher than the Control group (p < 0.05) on days 1, 3, and 7.

CONCLUSION: NaHS treatment increases the survival rate of rats after CA and ROSC by upregulating the expression and activation of BDNF and its receptor TrkB, and down-regulating p75NTR expression.