Prolonged inflammation leads to ongoing damage after spinal cord injury
| Autor: | Lidia Strużyńska, Barbara Marzec-Kotarska, Alexandra Lucas, Liqiang Zhang, Jordan R. Yaron, Greg J. Stanisz, Christian J. Kwiecien-Delaney, Jacek M. Kwiecien, John P. Karis, Wojciech Dabrowski, Lauren N. Schutz, Wendy Oakden, Grzegorz Sulkowski, B. Dabrowska-Bouta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Macroglial Cells Pathology Critical Care and Emergency Medicine Time Factors Physiology Anti-Inflammatory Agents Pathology and Laboratory Medicine Nervous System Severity of Illness Index Diagnostic Radiology Pathogenesis White Blood Cells Myelin 0302 clinical medicine Animal Cells Immune Physiology Medicine and Health Sciences Gliosis Spinal Cord Injury Immune Response Spinal cord injury Trauma Medicine Myelin Sheath Innate Immune System Multidisciplinary Radiology and Imaging Magnetic Resonance Imaging Astrogliosis medicine.anatomical_structure Spinal Cord Neurology Cytokines Medicine Anatomy Cellular Types Arachnoiditis medicine.symptom Traumatic Injury Research Article medicine.medical_specialty Histology Imaging Techniques Immune Cells Science Immunology Glial Cells Inflammation Research and Analysis Methods Neuroprotection Lesion 03 medical and health sciences Signs and Symptoms Diagnostic Medicine medicine Animals Humans Spinal Cord Injuries Blood Cells business.industry Macrophages Biology and Life Sciences Cell Biology Molecular Development medicine.disease Spinal cord Rats Neuroanatomy Disease Models Animal 030104 developmental biology Astrocytes Immune System business Neurotrauma 030217 neurology & neurosurgery Neuroscience Developmental Biology |
| Zdroj: | PLoS ONE, Vol 15, Iss 3, p e0226584 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates the severity of post-SCI inflammation and an ongoing controversy in the roles of astrocytes with studies identifying astrocytes as associated both with ongoing inflammation and damage as well as potentially having a protective role. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-α, IL-1β, IFN-γ and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |