Journal
JOURNAL OF NEUROINFLAMMATION
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1742-2094-10-83
Keywords
TLR; TRIF; MyD88; SAH; Microglia
Categories
Funding
- NINDS NIH HHS [NIH K08NS078048, K08 NS078048] Funding Source: Medline
Ask authors/readers for more resources
Background: Although microglia and the Toll-like receptor (TLR) pathway have long been thought to play a role in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), thus far only correlations have been made. In this study, we attempted to solidify the relationship between microglia and the TLR pathway using depletion and genetic knockouts, respectively. Methods: Subarachnoid hemorrhage was induced in TLR4-/-, TRIF-/-, MyD88-/- and wild type C57BL/6 mice by injecting 60 mu l of autologous blood near the mesencephalon; animals were euthanized 1 to 15 days after SAH for immunohistochemical analysis to detect microglia or apoptotic cells. Lastly, microglial depletion was performed by intracerebroventricular injection of clodronate liposomes. Results: On post operative day (POD) 7 (early phase SAH), neuronal apoptosis was largely TLR4-MyD88-dependent and microglial-dependent. By POD 15 (late phase SAH), neuronal apoptosis was characterized by TLR4-toll receptor associated activator of interferon (TRIF)-dependence and microglial-independence. Similarly, vasospasm was also characterized by an early and late phase with MyD88 and TRIF dependence, respectively. Lastly, microglia seem to be both necessary and sufficient to cause vasospasm in both the early and late phases of SAH in our model. Conclusion: Our results suggest that SAH pathology could have different phases. These results could explain why therapies tailored to aSAH patients have failed for the most part. Perhaps a novel strategy utilizing immunotherapies that target Toll like receptor signaling and microglia at different points in the patient's hospital course could improve outcomes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available