Defense Date

2013

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

Dong Sun

Abstract

Following traumatic brain injury (TBI), neuroinflammation contributes to the secondary injury. Microglia are the resident immune cells of the central nervous system (CNS), and when activated can exert either protective or detrimental effects on surrounding tissue. They are often segregated into subpopulations based on their type of activation, either pro- inflammatory (M1, classically activated), or anti-inflammatory (M2, alternatively activated). Minocycline, an anti-inflammatory drug, is known to be neuroprotective and to have effect on microglia. However, the effect of minocycline on subpopulations of inflammatory cells in the acute stage following injury is unclear. It is also unclear whether minocycline has a different treatment effect on injury-induced inflammatory responses in young and aged populations. In this study, we compared the effect of minocycline treatments on the microglial markers and the M2 subtype in both young (3-month-old) and aged (20-month-old) rats, sacrificed at three days after a moderate controlled cortical impact (CCI) injury. Minocycline treatments were either given beginning at 30 minutes post-injury or 4 hours post-injury for three days. Inflammatory cell markers ED1, OX6, and Iba1, as well as Arginase 1, a marker for alternatively activated macrophages/microglia, were used to label inflammatory cells. Staining intensity of each marker was analyzed in both the peri-lesion cortical tissue and the ipsilateral hippocampus regions. Our findings have found that 3-day minocycline treatment significantly attenuated TBI- induced inflammatory cell response especially in the aged rats. Minocycline treatment did not show any significant changes in the prevalence of the M2 phenotype. Our findings suggest that minocycline may exert its anti-inflammatory effect mostly on inhibition of M1 phenotype rather than promoting M2 phenotype.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

May 2013

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