Glial scar formation occurs in the human brain after ischemic stroke

Abstract

Reactive gliosis and glial scar formation have been evidenced in the animal model of ischemic stroke, but not in human ischemic brain. Here, we have found that GFAP, ED1 and chondroitin sulphate proteoglycans (CSPG) expression were significantly increased in the cortical peri-infarct regions after ischemic stroke, compared with adjacent normal tissues and control subjects. Double immunolabeling showed that GFAP-positive reactive astrocytes in the peri-infarct region expressed CSPG, but showed no overlap with ED1-positive activated microglia. Our findings suggest that reactive gliosis and glial scar formation as seen in animal models of stroke are reflective of what occurs in the human brain after an ischemic injury.

Keywords: glial scar; human; ischemic stroke; patients; reactive gliosis.

Figure 1

Glial scar formation in the peri-infarct region of the human brain after ischemic stroke. A. Human ischemic brain sections were stained with anti-CSPG. Representative images show that increased CSPG expression was predominantly found in the peri-infarct region and some were within the infarct area. Top panel: low magnification; Bottom panel: high magnification. B. Immunocytochemistry was performed using anti-GFAP. Representative images indicate that GFAP-positive reactive astrocytes significantly increased in the peri-infarct region after ischemic stroke in humans, compared with the normal region. Left panel: low magnification; Right panel: higher magnification. C. Immunocytochemistry was performed using anti-ED1. Representative images indicate that ED1-positive activated microglia were significantly increased in the peri-infarct region after ischemic stroke in humans, compared with the normal region. Left panel: low magnification; right panel: high magnification.

Figure 2

Increased expression of CSPG in reactive astrocytes in the peri-infarct region of human ischemic brain. A. Double immunocytochemistry was performed on the ischemic brain sections using anti-GFAP (red) and anti-CSPG (green). The images were recorded using a 2-photon confocal microscope. Representative images show that CSPG was predominantly expressed in GFAP-positive reactive astrocytes. B. Higher magnification view of insert in 2A. C. Confocal images of double-label immunohistochemistry on the ischemic brain section using anti-GFAP (red) and anti-ED1 (green). D. Higher magnification shows GFAP-positive reactive astrocytes (red) not co-localizing with ED1-postive activated micrglia (green). DAPI (blue) was used for nuclei counterstains.