Abstract Body: Background
Thoracoabdominal aneurysm (TAAA) repair can critically reduce spinal-cord blood flow, causing ischemic spinal cord injury (I-SCI) and paraplegia in some patients. The mechanisms causing paraplegia in I-SCI after aortic aneurysm repair are poorly understood, making objective management of this devastating complication difficult.

Objective
To characterize proteins in the cerebrospinal fluid (CSF) after endovascular thoracoabdominal aneurysm (TAAA) repair in search of novel biomarkers and therapeutic targets for paraplegia.

Methods
Analysis of CSF collected prior to and after endovascular in 37 patients (age 74±14.2 years, male 27) undergoing TAAA repair was analyzed using tandem mass- tag labelled proteomics and by ELISA. T2 weighted MRI was used to measure the spinal cord volume in patients with paraplegia and controls. A rodent model of I-SCI was used to investigate novel therapeutic targets identified by proteomic analysis.

Results
CSF of permanently paraplegic patients contained ~4-fold more soluble aquaporin-4 (41.8±19.2ng/ml, n=5), a key water channel protein in the blood-spinal cord barrier, than those who recovered from paraplegia (10.8±1.3ng/ml, n=7; P=0.01), or did not develop post-operative
paraplegia (10.8±1.2ng/ml, n=25; P=0.004). All permanently paraplegic patients had CSF aquaporin-4 levels >15ng/ml and greater spinal cord volumes on T2-weighted MRI (1.77±0.19 vs. 1.03±0.36; P=0.03) associated with spinal cord edema. Inhibition of aquaporin-4 in a rodent model of I-SCI preserved spinal neurons and glia in the dorsal horn and intermediate zones of white matter (P=0.0043) and was associated with gait preservation (P<0.001).

Conclusions
This study identified aquaporin-4 as a predictive biomarker and novel therapeutic target for permanent paraplegia in patients after TAAA repair. This represents a significant conceptual advancement in the management of I-SCI after TAAA repair.