Abstract
Brain injury causes astrocytes to become reactive (astrogliosis). In this study, we compared astrogliosis in acutely injured cortex and striatum of adult FVB/N mice induced by stereotaxic injection of ATP, a component of danger-associated molecular patterns (DAMPs). Interestingly, MR analysis showed that same amount of ATP induced smaller damage in the cortex than in the striatum. However, in histological analysis, thick and dense scar-like astrogliosis was found in the injured cortex near meninges within 2 wk., but not in other regions, including the striatum and even the cortex near the corpus callosum for up to 30 d. There was little regional difference in the number of Ki67(+)-proliferating astrocytes or mRNA expression of inflammatory cytokines. The most prominent difference between regions with and without scar-like astrogliosis was blood vessel formation. Blood vessels highly expressing collagen 1A1 formed densely near meninges, and astrocytes converged on them. In other regions, however, both blood vessels and astrocytes were relatively evenly distributed. Consistent with this, inhibition of blood vessel formation with the vascular endothelial growth factor (VEGF)-blocking antibody, Avastin, attenuated scar-like astrogliosis near meninges. These results indicate that region-specific astrogliosis occurs following brain injury, and that blood vessel formation plays a critical role in scar formation.
Highlights
Astrocytes in the injured brain undergo astrogliosis, characterized by a hypertrophic morphology and increased expression of glial fibrillary acidic protein (GFAP) [1, 2]
Expression levels of the astrocyte marker, GFAP, were relatively low in the cortex and striatum compared with other brain regions, including the olfactory bulb and hippocampus, among others, whereas that of another astrocyte marker, Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1), were largely similar in all brain regions examined (Fig. 1a)
We demonstrated that astrogliosis develops differently in different brain regions
Summary
Astrocytes in the injured brain undergo astrogliosis, characterized by a hypertrophic morphology and increased expression of glial fibrillary acidic protein (GFAP) [1, 2]. It manifests as mild to severe changes that have been suggested to depend on the extent of the injury. In the severely injured brain, In addition to astrocytes, several types of cells and/or molecules contribute to astrogliosis and/or scar formation. Glia and pericytes expressing neuron-glial antigen 2 (NG2), known as chondroitin sulfate proteoglycan 4 (CSPG4), contribute to scar formation [6,7,8]. CSPGs are well-known components of scar [9, 10]. It has recently been reported that type I collagen expressed in pericytes increases during scar
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