YKL-40 expression in traumatic brain injury: an initial analysis.
YKL-40 (chitinase 3-like protein 1) is expressed in a broad spectrum of inflammatory conditions and cancers. We have previously reported that YKL-40 levels are elevated in the cerebrospinal fluid (CSF) of macaques and humans with lentiviral encephalitis, as well as multiple sclerosis (MS). The current study assessed temporal CSF YKL-40 levels in subjects with severe traumatic brain injury (TBI; Glasgow Coma Scale [GCS] score <or=8). We also evaluated temporal expression of YKL-40 after parasagittal controlled cortical impact (CCI) injury over the parietal cortex (2.8 mm deep, 4 m/sec). We demonstrate that CSF YKL-40 levels are elevated after acute TBI, and that YKL-40 levels are higher in patients who died following injury than in patients who survived. YKL-40 levels significantly correlate with CSF levels of inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as the inflammatory marker C-reactive protein (CRP). After CCI, in situ hybridization (ISH) showed that YKL-40 transcription is primarily associated with reactive astrocytes in pericontusional cortex. Tissue YKL-40 transcription time course analysis after CCI showed that YKL40 transcription in astrocytes began 1 day after injury, remained elevated for several days, and then declined by day 12. Similarly to our temporal CSF measurements in humans, YKL-40 induction after CCI is coincident with IL-1beta expression. Taken together these findings demonstrate that YKL-40 is induced in astrocytes during acute neuroinflammation, is temporally related to inflammatory mediator expression, and may be a useful biomarker for understanding secondary injury and for patient prognosis.
Bonneh-Barkay
Dafna
D
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. bonnehbarkayd@upmc.edu
Zagadailov
Pavel
P
Zou
Huichao
H
Niyonkuru
Christian
C
Figley
Matthew
M
Starkey
Adam
A
Wang
Guoji
G
Bissel
Stephanie J
SJ
Wiley
Clayton A
CA
Wagner
Amy K
AK
D054392:Adipokines; D000293:Adolescent; D000328:Adult; D000818:Animals; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000401:mortality; D000071451:Chitinase-3-Like Protein 1; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000134:cerebrospinal fluid* / Q000235:genetics; D006801:Humans; D037102:Lectins / Q000032:analysis / Q000134:cerebrospinal fluid* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins