Hyperglycemia aggravates spinal cord injury through endoplasmic reticulum stress mediated neuronal apoptosis, gliosis and activation.

BACKGROUND

Hyperglycemia has been shown to influence prognostic outcome of spinal cord injury (SCI). However, the corresponding mechanism is not very clear.

AIM: This study is expected to explore the role of endoplasmic reticulum (ER) stress in hyperglycemia aggravated SCI.

METHODS

Hyperglycemia was established in rats by intraperitoneal (i.p.) injection of streptozotocin. SCI was performed at the T10 of spinal cord through weight dropping. ER stress was suppressed by oral gavage of 4-PBA. ER stress, histological change of the injured spinal cords, neuronal apoptosis, demyelination, glial proliferation, inflammatory factor production, blood-spinal cord barrier (BSCB) permeability, TJ (Occludin, Claudin5) and AJ (β-catenin, P120) protein degradation, and locomotor recovery were determined using western blotting, immunohistochemistry, HE staining, Evan's Blue assay, BBB scores and inclined plane test, respectively. In vitro, rat spinal cord neurons cells (RSCNCs) and cerebral microvascular endothelial cells (RCMECs) were stimulated with high glucose (HG) and/or thapsigargin (TG). The effects of HG and/or TG on RSCNCs apoptosis, and AJ and TJ expression by RCMECs were evaluated with flow cytometry and western blotting, respectively.

RESULTS

Hyperglycemic rats exhibited enhanced ER stress, increased neuronal apoptosis, aggravated demyelination, increased glial proliferation and inflammatory factors secretion, more serious BSCB disruption and disturbed locomotor recovery. ER stress inhibition alleviated hyperglycemia induced adverse effect on neuronal apoptosis and BSCB permeability, whereas showed little influence on glial activation and inflammation.

CONCLUSION

ER stress was aggravated in hyperglycemic rats after SCI, and subsequently promoted neuronal apoptosis and BSCB disruption in rats.