To evaluate the changes in activation of γ-aminobutyric acid(GABA)signaling pathway during ventilator-induced brain injury in rats.

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 GABA_A receptors(by Western blot). Morris water maze test was performed on 2nd day after the end of ventilation.

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 GABA_A 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 GABA_A 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).

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.

gamma-Aminobutyric acid; Respiration, artificial; Brain injuries