| First Author | Koh HS | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6340 | PubMed ID | 25790768 |
| Mgi Jnum | J:221874 | Mgi Id | MGI:5641786 |
| Doi | 10.1038/ncomms7340 | Citation | Koh HS, et al. (2015) The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia. Nat Commun 6:6340 |
| abstractText | Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1alpha-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1alpha-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases. |
