Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults

Reeves, C., Jardim, A.P., Sisodiya, S.M., Thom, M. and Liu, J. 2019. Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults. Neuropathology and Applied Neurobiology. 45 (6), pp. 609-627 NAN-2018-0107.R1. https://doi.org/10.1111/nan.12539

TitleSpatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults
TypeJournal article
AuthorsReeves, C., Jardim, A.P., Sisodiya, S.M., Thom, M. and Liu, J.
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) were 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-localisation 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-localisation 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 suggests functional alterations during temporal stages of brain repair.

KeywordsBrain injury
electrodes
pericytes
glial scar
progenitors
connexin
epilepsy
Article numberNAN-2018-0107.R1
JournalNeuropathology and Applied Neurobiology
Journal citation45 (6), pp. 609-627
ISSN0305-1846
Year2019
PublisherWiley
Accepted author manuscript
Digital Object Identifier (DOI)https://doi.org/10.1111/nan.12539
Publication dates
Published online12 Jan 2019
Published in printOct 2019
FunderMRC (Medical Research Council)
Supplementary data or files
File

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