Spinal cord injury induces differential expression of the profibrotic semaphorin 7A in the developing and mature glial scar.

Semaphorin 7A (Sema7A) is involved in the formation of the central nervous system during development by operating axon guidance and neuronal migration. We investigated the expression of the TGFß-inducible Sema7A following spinal cord injury (SCI). After SCI, Sema7A(+) cells accumulated specifically in lesion areas resulting in significantly enhanced Sema7A expression at the injury site (P < 0.0001). During the first days lesional Sema7A expression was confined to neurons, ballooned neurite fibers/retraction bulbs, and endothelial cells. At day 7, we observed Sema7A expression by components of the glial scar, such as reactive astrocytes and pronounced extracellular Sema7A deposition. In the direct perilesional rim, Sema7A(+) astrocytes coexpressed the activation-associated intermediate filament vimentin. In the injured spinal cord, numbers of Sema7A(+) cells reached maximum levels at day 14. The restricted accumulation of Sema7A(+) reactive astrocytes and Sema7A deposition in fibronectin(+) extracellular matrix territories suggests a participation of the fibrostimulatory Sema7A in the developing and maturating scar following SCI. In addition, Sema7A appears to be marker a for astrocyte activation.

Non-resolving aspects of acute inflammation after spinal cord injury (SCI): indices and resolution plateau.

Inflammatory resolution is an active, highly regulated process already encoded at the onset of inflammation and required to prevent the transition into chronic inflammation associated with spreading of tissue injury and exacerbated scarring. We introduce objective, quantitative measurements [resolution indices (R(i) ) and resolution plateau (R(P) )] to characterize inflammatory resolution and to determine the persistence ("dwell time") of differential leukocyte subpopulations at the lesion site after acute experimental spinal cord injury (SCI). The cell type-specific resolution interval R(i) (time between maximum cell numbers and the point when they are reduced to 50%) ranges from 1.2 days for neutrophils, 1.5 days for T lymphocytes, to 55 days for microglia/macrophages. As the resolution interval neglects exiting cell trafficking in the later period of resolution (49%-0% of lesional cells), we introduced the R(P) , a marker for the persisting, chronified leukocyte subsets, which are likely to participate in late degeneration and non-resolving inflammation. Here, we identify the acute inflammatory response in central nervous system (CNS) lesions as partly non self-limiting. Both extended resolution intervals (reduced leukocyte clearance) and elevated plateaus (permanent lesional cell numbers) provide quantitative measures to characterize residual, sustained inflammation and define cognate timeframes of impaired resolution after acute SCI.