Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute
spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after
spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor,
4-phenylbutyric acid, and autophagy inhibitor,
chloroquine, were respectively or combinedly administrated in the model of acute
spinal cord injury rats. At day 1 after
spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of
trauma. Inhibition of ER stress by treating with
4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ)
proteins and reduced autophagy activation after
spinal cord injury. On the contrary, inhibition of autophagy by treating with
chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ
proteins and enhanced ER stress after
spinal cord injury. When
4-phenylbutyric acid and
chloroquine were combinedly administrated in
spinal cord injury rats,
chloroquine abolished the blood-spinal cord barrier protective effect of
4-phenylbutyric acid by exacerbating ER stress after
spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute
spinal cord injury. The present study illustrates that ER stress induced by
spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by
spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in acute
spinal cord injury.