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

C Reeves,J Y W Liu,S M Sisodiya,M Thom,A Pradim‐Jardim

doi:10.1111/nan.12539

Abstract

AimsUnderstanding 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.MethodsIn 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.ConclusionsThese 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.

Highlights

There is a fine balance in repair processes following brain injury between the beneficial effects that limit tissue damage and restore homeostasis and the long-term detrimental effects that can follow glial scar formation, such as impediment to axonal regeneration and increased risk of seizures [1,2]
Pericytes and glial cell reactions in intracranial recordings (ICR) injuries Qualitative analysis: Nestin/plateletderived growth factor receptor beta (PDGFRb): In acute ICR lesions, multipolar nestin+ cells and nestin+ cells with elongated processes became prominent between capillaries in Zones 1 and 2 (Figure 2A–C); in Zone 3, nestin labelling was noted mainly in capillaries (Figure 2J)
Using ICR penetrating injuries in human tissues, we investigated the spatiotemporal dynamics of PDGFRb+ cells and its relationship with other glial cell types such as GFAP and nestin-expressing cells in the formation of a glial scar

Summary

Introduction

There is a fine balance in repair processes following brain injury between the beneficial effects that limit tissue damage and restore homeostasis and the long-term detrimental effects that can follow glial scar formation, such as impediment to axonal regeneration and increased risk of seizures [1,2]. Understanding which endogenous progenitor cell types contribute to tissue As the time interval between initial electrode placement and subsequent tissue resection is precisely known (but variable between cases) and the injury is localized, this provides a unique spectrum from acute injuries to chronic scars, spanning from 3 days to over 1-year-old injuries, to study spatiotemporal processes in human brain repair. A further possibility, in view of the observed intimate relationship of new capillaries and glia in the repair process, is that nestin-expressing cells are recruited from progenitors in the perivascular niche, including pericytes with capacity for neuroectodermal differentiation [9]

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Conclusion