Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-α/TACE in focal cerebral ischemia in mice
2011

TIMP-3 and Oligodendrocyte Death in Ischemic Brain Injury

Sample size: 89 publication 10 minutes Evidence: high

Author Information

Author(s): Yang Yi, Jalal Fakhreya Y, Thompson Jeffrey F, Walker Espen J, Candelario-Jalil Eduardo, Li Lu, Reichard Ross R, Ben Chi, Sang Qing-Xiang, Cunningham Lee Anna, Rosenberg Gary A

Primary Institution: University of New Mexico Health Sciences Center

Hypothesis

TIMP-3 contributes to oligodendrocyte death during focal cerebral ischemia.

Conclusion

TIMP-3 deficiency protects immature oligodendrocytes from apoptosis in ischemic conditions.

Supporting Evidence

  • TIMP-3 expression was increased in wild type reactive astrocytes.
  • Loss of OL-like cells was detected at 72 h only in wild type ischemic white matter.
  • TUNEL assay showed greater cell death in wild type compared to knockout mice.
  • Significantly higher levels of cleaved caspase-3 were found in wild type white matter.
  • More microglia/macrophages were present in wild type than in knockout mice.

Takeaway

This study found that a protein called TIMP-3 helps cause the death of certain brain cells when there is a lack of blood flow, but without it, those cells are safer.

Methodology

Mice underwent middle cerebral artery occlusion followed by reperfusion, and cell death was assessed using stereology and TUNEL assays.

Potential Biases

Potential bias in the interpretation of immunohistochemical results and the selection of animal models.

Limitations

The study primarily focused on immature oligodendrocytes and may not fully represent other cell types affected by ischemia.

Participant Demographics

Eighty-nine male mice aged 10-12 weeks were used in the study.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1742-2094-8-108

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication