The microglial activation profile and associated factors after experimental spinal cord injury in rats

Abstract

BackgroundSpinal cord injury (SCI) has imposed a great impact on the quality of life of patients due to its relatively young age of onset. The pathophysiology of SCI has been proven to be complicated. Microglia plays an important role in neuroinflammation and second injuries after SCI. Different environment and other factors may determine the microglial activation profile and what role they play. However, neither accurate time-course profiles of microglial activation nor influence factors have been demonstrated in varied SCI models.MethodsA rat compressive SCI model was used. Microglial activation profile and contents of inflammatory factors including IL-1β, IL-6 and TNF-α were detected. Myelination status as well as levels of iron and glutamate concentration, adenosine triphosphate (ATP) and potassium are also assessed.ResultsOur results showed that the activated microglia participating in immune-mediated responses peaked at day 7 post SCI and gradually decreased during the following 3 weeks. Contrarily, myelination and oligodendroglia showed an opposite trend, indicating that microglia may be a key factor partly through inflammatory reaction. Iron and glutamate concentration were found to be the highest at day 7 after SCI while both ATP and potassium reached a low valley at the same time.ConclusionThese findings showed a microglial activation profile and the alterations of associated factors after experiment SCI model. Moreover, our data suggest that high iron and glutamate concentration may be released by damaged oligodendroglia and contribute to the activation of microglial after SCI.

Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest

“…Pathological changes between CA and ROSC may be related to the degree of neurological dysfunction. Microglia, resident immune cells in the central nervous system (CNS), are increased in number and morphologically activated at an early stage after spinal cord injury [35,36], which contributes to neuroinflammation and onset of neuronal damage by releasing large amount of inflammatory cytokines and ROS [37,38]. Similar to previous studies, our results showed that ACA resulted in significant microglia activation in the ventral horn of the lumbar spinal cord.…”

Cell and Tissue Instructive Materials for Central Nervous System Repair

“…Thus, microglia are activated and together with the infiltrating monocytes/macrophages into the injured site release a panel of cytokines, such as TNF-α, IL-1β, and IL-1α, which further worsen the local environment and contribute to a massive damage of the surrounding tissue. [19,20] Other events like ischemia, glutamate excitotoxicity, and apoptosis contribute to the formation of the glial scar that is surrounded by reactive astrocytes, creating an inhibitory microenvironment for axonal regrowth or tissue regeneration. [21] Until today there is no effective treatment to tackle SCI.…”

Cytokine profile as a marker of cell damage and immune dysfunction after spinal cord injury

“…The functions of the immune system change significantly as the immediate post-traumatic phase after the injury progresses to a chronic phase. The loss or dysfunction of vegetative innervation in the lymphatic and endocrine tissues causes immune response disorders that last quite a long time after the initial trauma [ 84 ]. The main manifestations of such disorders are immune depression and the autoimmune process [ 83 ], although inflammatory reactions also remain pathogenetically significant.…”