Induction of angiopoietin-2 after spinal cord injury.
Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have opposing effects on blood vessels, with Ang-2 being mainly induced during the endothelial barrier breakdown. It is known that spinal cord injury (SCI) induces lasting decreases in Ang-1 levels, underlying endothelial barrier disruption, but the expression of Ang-2 in spinal cord injury has not been studied. We characterized Ang-2 after SCI using a clinically relevant rat model of contusion SCI. We found that SCI induces marked and persistent upregulation of Ang-2 (up to 10 weeks after SCI), which does not reflect well-characterized temporal profile of the blood-spinal cord barrier (BSCB) breakdown after SCI, and thus suggests other role(s) for Ang-2 in injured spinal cords. Furthermore, we also found that higher Ang-2 levels were associated with more successful locomotor recovery after SCI, both in SCI rats with markedly better spontaneous motor recovery and in SCI rats receiving a neuroprotective pharmacological intervention (amiloride), suggesting a beneficial role for Ang-2 in injured spinal cords. Immunocytochemical analyses revealed that Ang-2 was not induced in endothelial cells, but in perivascular and non-vascular cells labeled with glial fibrillary acidic protein (GFAP) or with chondroitin sulfate proteoglycan (NG2). Therefore, it is unlikely that induction of Ang-2 contributes to vascular dysfunction underlying functional impairment after SCI, but rather that it contributes to the beneficial pro-angiogenic and/or gliogenic processes underlying recovery processes after SCI.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1072, USA.
J C
JC
Durham-Lee
Y
Y
Wu
V U L
VU
Mokkapati
A A
AA
Paulucci-Holthauzen
O
O
Nesic
D000584:Amiloride / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000096:biosynthesis; D042702:Angiopoietin-2 / Q000096:biosynthesis*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology; D015153:Blotting, Western; D002809:Chondroitin Sulfates; D004232:Diuretics / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D004232:Diuretics; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D000584:Amiloride; D002809:Chondroitin Sulfates