Role for mammalian chitinase 3-like protein 1 in traumatic brain injury.
Traumatic brain injury (TBI) is accompanied by inflammatory infiltrates and CNS tissue response. The astrocytosis associated with TBI has been proposed to have both beneficial and detrimental effects on surviving neural tissue. We recently observed prominent astrocytic expression of YKL-40/chitinase 3-like protein 1 (CHI3L1) associated with severity of brain injury. The physiological role of CHI3L1 in the CNS is unknown; however, its distribution at the perimeter of contusions and temporal course of expression suggested that in TBI it might be an important component of the astrocytic response to modulate CNS inflammation. To address this hypothesis, we used serially sectioned brains to quantitatively compare the neuropathological outcomes of TBI produced by controlled cortical impact in wild type (WT) and chi3l1 knockout (KO) mice where the murine YKL-40 homologue, breast regression protein 39 (BRP-39/CHI3l1), had been homozygously disrupted. At 21 days post-injury, chi3l1 KO mice displayed greater astrocytosis (increased GFAP staining) in the hemispheres ipsilateral and contralateral to impact compared with WT mice. Similarly, Iba1 expression as a measure of microglial/macrophage response was significantly increased in chi3l1 KO compared with WT in the hemisphere contralateral to impact. We conclude that astrocytic expression of CHI3L1 limits the extent of both astrocytic and microglial/macrophage facets of neuroinflammation and suggests a novel potential therapeutic target for modulating neuroinflammation.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clayton A
CA
Wiley
Dafna
D
Bonneh-Barkay
C Edward
CE
Dixon
Andrew
A
Lesniak
Guoji
G
Wang
Stephanie J
SJ
Bissel
Patrick M
PM
Kochanek
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D000071451:Chitinase-3-Like Protein 1; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism
C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse
BRP-39; chitinase 3-like protein 1; controlled cortical impact; neuroinflammation; traumatic brain injury