Induction of angiopoietin-2 after spinal cord injury

• Published in: Neuroscience 2012-01, Vol.202, p.454-464
• Main Authors: Durham-Lee, J.C, Wu, Y, Mokkapati, V.U.L, Paulucci-Holthauzen, A.A, Nesic, O
• Format: Article
• Language: English
• Subjects: amiloride; Amiloride - pharmacology; Ang-1; Ang-2; Angiopoietin-1 - biosynthesis; Angiopoietin-2 - biosynthesis; Animals; Biological and medical sciences; Blood Vessels - metabolism; Blood-Brain Barrier - physiology; Blotting, Western; Chondroitin Sulfates; Diuretics - pharmacology; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein; Immunohistochemistry; Male; Microscopy, Confocal; Motor Activity - drug effects; motor recovery; Nerve Tissue Proteins - isolation & purification; Nerve Tissue Proteins - metabolism; Neurology; NG2; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord - anatomy & histology; Spinal Cord - metabolism; Spinal Cord Injuries - metabolism; spinal cord injury; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.09.058

Abstract 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.