Characterization of Chitinase 3-like protein 1 spatiotemporal distribution in human post-traumatic brain contusions and other neuropathological scenarios.

Abstract

Chitinase 3-like protein 1 (CHI3L1) is emerging as a promising biomarker for assessing intracranial lesion burden and predicting prognosis in traumatic brain injury (TBI) patients. Following experimental TBI, Chi3l1 transcripts were detected in reactive astrocytes located within the pericontusional cortex. However, the cellular sources of CHI3L1 in response to hemorrhagic contusions in human brain remain unidentified. Hence, we examined a comprehensive collection of histologically defined acute and subacute human cerebral contusions with various surgical intervals using immunohistochemistry, validated through double immunofluorescence for markers such as GFAP, NeuN, MBP, and Iba-1, along with Fluoro-Jade C histofluorescence staining. CHI3L1 was found at meningeal interfaces, showing significant thickening of subpial glial plate. Paradoxically, CHI3L1-positive astrocytes were identified in neuroanatomical locations distant from hemorrhagic foci, where numerous eosinophilic ischemic neurons also exhibited CHI3L1 immunoreactivity. CHI3L1 immunostaining extended into white matter tracts and highlighted various phagocytic or activated microglia forms after delayed surgical decompressions. Given these findings, we advise against using CHI3L1 as a reactive astrogliosis marker due to its expression in multiple cell types, including astrocytes, neurons, oligodendrocytes, ependymocytes, leptomeningeal cells, microglia, and blood vessels. This non-selective response underscores the potential for CHI3L1 elevation patterns in biofluids to reflect the overall lesion burden extent.