Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Haider, T; Höftberger, R; Rüger, B; Mildner, M; Blumer, R; Mitterbauer, A; Buchacher, T; Sherif, C; Altmann, P; Redl, H; Gabriel, C; Gyöngyösi, M; Fischer, MB; Lubec, G; Ankersmit, HJ.
The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats.
Exp Neurol. 2015; 267(3):230-242
Doi: 10.1016/j.expneurol.2015.03.013
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- Co-Autor*innen der Med Uni Graz
- GABRIEL Christian
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- Abstract:
- After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68(+) cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats. Copyright © 2015. Published by Elsevier Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, CD - metabolism
- Antigens, Differentiation, Myelomonocytic - metabolism
- Aorta - metabolism
- Aorta - pathology
- Cell- and Tissue-Based Therapy -
- Chemokine CXCL1 - metabolism
- Cytokines - blood
- Disease Models, Animal -
- Gene Expression Regulation - drug effects
- Humans -
- Inflammation - etiology
- Inflammation - therapy
- Leukocytes, Mononuclear - chemistry
- Leukocytes, Mononuclear - metabolism
- Male -
- Motor Activity - physiology
- Nitric Oxide Synthase Type II - metabolism
- Oxidative Stress - physiology
- Rats -
- Rats, Sprague-Dawley -
- Recovery of Function - physiology
- Spinal Cord - metabolism
- Spinal Cord - pathology
- Spinal Cord Injuries - blood
- Spinal Cord Injuries - complications
- Spinal Cord Injuries - therapy
- Time Factors -
- Vascular Endothelial Growth Factor A - immunology
- Find related publications in this database (Keywords)
- Spinal cord injury
- Inflammation
- Traumatic spinal cord injury
- MNC-secretome
- Oxidative stress
- PBMCs
- Secondary damage