Changes in activation of γ-aminobutyric acid signaling pathway during ventilator-induced brain injury in rats

Abstract

Objective To evaluate the changes in activation of γ-aminobutyric acid(GABA)signaling pathway during ventilator-induced brain injury in rats. Methods Thirty-six pathogen-free adult male Sprague-Dawley rats, weighing 280-320 g, were divided into 3 groups(n=12 each)using a random number table: low tidal volume group(LV group), ventilation with high tidal volume for 2 h group(HV1 group)and ventilation with high tidal volume for 6 h group(HV2 group). The rats were mechanically ventilated for 2 h with the tidal volume set at 10 ml/kg and the respiratory rate 40 breaths/min in group LV.The rats were mechanically ventilated for 2 h with the tidal volume set at 40 ml/kg and the respiratory rate 40 breaths/min in group HV1.The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml/kg and the respiratory rate 40 breaths/min in group HV2.Blood samples were collected at the end of ventilation for determination of serum neuron-specific enolase(NSE)and S100β protein concentrations by enzyme-linked immunosorbent assay.Six rats were then sacrificed and their brains were removed for determination of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)contents(by enzyme-linked immunosorbent assay)and expression of glutamic acid decarboxylase(GAD)and GABAA receptors(by Western blot). Morris water maze test was performed on 2nd day after the end of ventilation. Results Compared with group LV, the serum concentrations of NSE and S100β protein and contents of IL-1β and TNF-α were significantly increased, the expression of GAD and GABAA receptors was up-regulated, the escape latency was prolonged, and the percentage of swimming distance at the original platform was decreased in HV1 and HV2 groups(P<0.05). Compared with group HV1, the serum concentrations of NSE and S100β protein and contents of IL-1β and TNF-α were significantly increased, the expression of GAD and GABAA receptors was up-regulated, the escape latency was prolonged, and the percentage of swimming distance at the original platform was decreased in group HV2(P<0.05). Conclusion Activation of GABA signaling pathway is enhanced during ventilator-induced brain injury, which may be involved in the pathophysiological mechanism of ventilator-induced brain injury in rats. Key words: gamma-Aminobutyric acid; Respiration, artificial; Brain injuries