Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults. (2nd April 2019)

• Record Type: Journal Article
• Authors: Reeves, C.; Pradim‐Jardim, A.; Sisodiya, S. M.; Thom, M.; Liu, J. Y. W.
• Is Part Of: Neuropathology & applied neurobiology. Volume 45:Number 6(2019)
• Page Start: 609
• Page End: 627
• Publication Date: 2019-04-02
• Subjects: Brain injury -- glial scar -- pericytes -- progenitors; Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12539
• Languages: English
• ISSNs: 0305-1846

Abstract

Abstract : Aims: Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar‐forming nestin‐expressing cells. We now explore the relationship between nestin‐expressing cells, PDGFRβ + pericytes and Olig2 + glia, including their proliferation and functional maturation. Methods: In 32 cases, ranging from 3 to 461 days post injury (dpi), immunohistochemistry for PDGFRβ, nestin, GFAP, Olig2, MCM2, Aquaporin 4 (Aq4), Glutamine Synthetase (GS) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (LI) and cellular co‐expression at the injury site compared to control regions. Results: PDGFRβ labelling highlighted both pericytes and multipolar parenchymal cells. PDGFRβ LI and PDGFRβ + /MCM2 + cells significantly increased in injury Zones at 10–13 dpi with migration of pericytes away from vessels with increased co‐localization of PDGRFβ with nestin compared to control regions ( P < 0.005). Olig2 + /MCM2 + cell populations peaked at 13 dpi with significantly higher cell densities at injury sites than in control regions ( P < 0.01) and decreasing with dpi ( P < 0.05). Cx43 LI was reduced in acute injuries but increased with dpi ( P < 0.05) showing significant cellular co‐localization with nestin and GFAP ( P < 0.005 and P < 0.0001) but not PDGFRβ. Conclusions: These findings indicate that PDGFRβ + and Olig2 + cells contribute to the proliferative fraction following penetrating brain injuries, with evidence of pericyte migration. Dynamic changes in Cx43 in glial cell types with dpi suggest functional alterations during temporal stages of brain repair.