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Neuroinflammation after traumatic injury to the developing brain

Vanya Goranova Stefovska, Marco Sifringer, Stefanie Endesfelder, Chrysanthy Ikonomidou

Abstract

PURPOSES: Mechanical trauma to the developing rodent brain induces a diffuse secondary neuroapoptosis associated with infiltration of immune cells, local and systemic increased levels of proinflammatory mediators. Our aim was to study their expression, cellular localization, distribution pattern and time course in various brain regions.

 

MATERIALS AND METHODS: 7-day-old Wistar rats and C57/BL6 mice were subjected to cortical trauma. Animals were sacrificed at defined time points - from 2 h to 14 days following trauma. Brain tissues were processed for molecular analyses, single or double indirect peroxidase/fluorescence immunohistochemistry for apoptotic cell death, microglia and interleukin (IL)-1ß/IL-18.

 

RESULTS: Apoptotic neuronal cell death detected by TUNEL was found at distant regions to trauma site mainly ipsilateral from 6 h to 5 days later. A substantial activation of ED1+ microglia occurred at the site of primary and secondary damages. It was first evident at 12 h, peaked at 36-48 h and decreased significantly after 5 days. A marked increase of mRNA, protein levels and imunohistochemical expression of two pro-inflammatory cytokines, interleukin (IL)-1ß and IL-18, was found from 2 h to 5 days following trauma. Mice deficient in IL-18 (IL-18−/−) were protected against post-traumatic brain damage.

 

CONCLUSIONS: Brain trauma leads to neuroinflammation expressed by microglial activation and an increase in IL-1ß and IL-18. Activated microglia are one of the main cellular sources of elevated levels for both cytokines. They are probably involved in and help sustain apoptotic neurodegeneration over several days after trauma. This finding might define microglia and IL-1ß/IL-18 as potential post-traumatic therapeutic targets.


Keywords

neuroapoptosis; ED1+ cells, IL-1ß; IL-18; trauma; immature brain

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DOI: http://dx.doi.org/10.14748/ssm.v47i1.829

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About The Authors

Vanya Goranova Stefovska
Dept. of Anatomy, Histology and Embryology, Medical University, Varna
Bulgaria

Marco Sifringer
Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum
Germany

Department of Anesthesiology and Intensive Care Medicine

Stefanie Endesfelder
Campus Virchow-Klinikum

Department of Neonatology, Charité-Universitätsmedizin Berlin

Chrysanthy Ikonomidou
University of Wisconsin, Madison
United States

Department of Neurology

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