Reena Kumari, Gabrielle V Hammers, Robert H Hammons, Andrew N Stewart, Steven M MacLean, Tracy Niedzielko, Lonnie E Schneider, Candace L Floyd, John C Gensel
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引用次数: 0
Abstract
Objective: Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model.
Methods: Adult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury.
Results: SCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing at 6 weeks with no difference between sexes. Immunohistological evaluations of spinal cord tissue at 2 days and 6 weeks post-injury revealed intraspinal microglia/macrophage (IBA-1, CD68) and lymphocyte responses (T-cells (CD3) and B-cells (CD79a)) consistent with observations in rodents and humans. Astrocyte (GFAP) immunoreactivity was observed within the lesion core at 6 weeks in contrast to observations in rodents. No differences were seen for astrocytes, microglia, macrophages, B-cells, and neutrophil infiltration between males and females. Intraspinal CD3 + T-cell counts and T-cell microclusters were significantly higher in females compared to males 6 weeks post-injury. Interestingly, we observed a similar significant increase in intraspinal CD3 + T-cell accumulation in female vs. male mice at 6 weeks post-thoracic contusion SCI.
Interpretation: Our observations indicate that sex is a potential biological variable for T-cell infiltration and may contribute to sex-based differences in SCI pathophysiology and recovery outcomes.
期刊介绍：
The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes.
Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems.
The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.
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