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January 1, 2010Journal of Neuroinflammation293 citationsOpen Access

In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases

DBDafna Bonneh‐BarkayGWGuoji WangASAdam Starkey

Key Result

Cerebrospinal fluid CHI3L1 levels were significantly elevated in multiple sclerosis patients compared to young healthy controls (median 281 vs 109 ng/ml, p=0.0007), with transcription predominantly associated with reactive astrocytes.

Study Design

Type

Cross-Sectional (n=78)

Multicenter

Yes

PICO

P
Population
78 cerebrospinal fluid and brain tissue samples from patients with multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, and healthy controls to evaluate CHI3L1 expression.
E
Exposure / Comparator
Neurological diseases (e.g., multiple sclerosis) vs Healthy controls
O
Primary Outcome
Cerebrospinal fluid CHI3L1 concentration (ng/ml), p=0.0007

Main Result

Absolute Event Rate: 281% vs 109%

p-value: p=0.0007

Limitations

  • Small sample sizes for each disease category
  • Cross-sectional nature of the human samples limits temporal analysis
  • Discrepancy between in vitro macrophage and in vivo astrocyte CHI3L1 expression remains unresolved

Abstract

BACKGROUND: CHI3L1 (YKL-40) is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF) of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes. METHODS: In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases. RESULTS: ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS) patients as well as mild elevation with aging. In situ hybridization (ISH) showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts. CONCLUSIONS: Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells.

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Cite This Study

Bonneh‐Barkay et al. (2010) conducted a cross-sectional in Neurological diseases (n=78). Neurological diseases (e.g., multiple sclerosis) vs. Healthy controls was evaluated on Cerebrospinal fluid CHI3L1 concentration (ng/ml) (p=0.0007). Cerebrospinal fluid CHI3L1 levels were significantly elevated in multiple sclerosis patients compared to young healthy controls (median 281 vs 109 ng/ml, p=0.0007), with transcription predominantly associated with reactive astrocytes.

synapsesocial.com/papers/6a2b30cd45177ee77d93b58fhttps://doi.org/10.1186/1742-2094-7-34
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