PTPRO inhibition shields the blood–brain barrier in mouse endotoxemia
- LPS raised PTPRO levels in the brain tissue and cerebral endothelial cells of endotoxemic mice; PTPRO overexpression drove F-actin reorganization, stress fibres and intercellular gaps.
- PTPRO knockdown, deficiency or the inhibitor Pi reversed these changes and reduced thrombin-induced permeability in brain endothelial cells.
- In the LPS mouse model, Pi lessened BBB leakage, supporting PTPRO as a handle on septic encephalopathy.
💡 Points Based on the abstract
Genetic and pharmacological arms agree, which is more than most phosphatase papers manage. What worries me is the model: a single LPS challenge is acute and gives no sense of whether a drug given after the insult, when a septic patient actually arrives, still works. Phosphatase inhibitors are also notoriously hard on selectivity, so I'd ask for the Pi profile across related PTPs.