The evolution of ischemic spinal cord injury in function, cytoarchitecture, and inflammation and the effects of adenosine A2A receptor activation.
OBJECTIVE
Spinal cord ischemia/reperfusion injury involves multiple factors that may be modulated by adenosine A 2A receptor activation. This study defines injury progression in terms of function, cytoarchitecture, and inflammation and assesses whether adenosine A 2A receptor activation by ATL-146e limits injury progression.


METHODS
Mature swine were divided into 3 groups: sham thoracotomy, IR (30 minutes of ischemia followed by reperfusion), and ATL (ischemia/reperfusion with ATL-146e administration for the first 3 hours of reperfusion). Subgroups were killed at 0, 3, 6, 12, 24, and 48 hours after reperfusion. Function was followed up with Tarlov scores. Spinal cord tissue was evaluated for neuronal viability, microtubule-associated protein-2 immunohistochemistry, and neutrophil sequestration (myeloperoxidase assay). Spinal cord tissue, cerebrospinal fluid, and serum were evaluated for tumor necrosis factor-alpha by enzyme-linked immunosorbent assay.


RESULTS
Function was significantly impaired at 24, 36, and 48 hours in the IR group compared with the sham and ATL groups ( P < .05). Neuronal viability and microtubule-associated protein-2 staining were significantly preserved in the sham and ATL groups compared with the IR group at 24 and 48 hours ( P < .05). Spinal cord myeloperoxidase levels were significantly higher in the IR group than in the sham and ATL groups at 24 and 48 hours. Although negligible in serum and cerebrospinal fluid, tumor necrosis factor-alpha levels in the spinal cord peaked significantly higher in the IR group compared with the sham and ATL groups at 6 and 24 hours ( P < .05).


CONCLUSIONS
Spinal cord ischemia/reperfusion induced changes in neutrophil sequestration, microtubule-associated protein-2 expression, and neuronal viability within 24 hours of reperfusion. Spinal cord tumor necrosis factor-alpha increased significantly by 6 to 12 hours after reperfusion. Adenosine A 2A receptor activation attenuates spinal cord inflammation, which may be critical for the preservation of neuronal function and cytoarchitecture after ischemia/reperfusion.
Reece
T Brett
TB
Department of Surgery, University of Virginia Health System, PO Box 801359, Charlottesville, VA 22908, USA. tbr5q@virginia.edu
Okonkwo
David O
DO
Ellman
Peter I
PI
Warren
Patrick S
PS
Smith
Robert L
RL
Hawkins
A Stewart
AS
Linden
Joel
J
Kron
Irving L
IL
Tribble
Curtis G
CG
Kern
John A
JA
D000818:Animals; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D043683:Receptors, Adenosine A2; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000503:physiopathology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D043683:Receptors, Adenosine A2; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase