I am looking at the effects of a compound on blood-brain barrier integrity. Preliminary results indicate that the compound improves tight junction expression in aged mice. I am looking for a way to induce BBB leakage in young mice to see if the compound can improve functional outcomes. I am aware that head trauma is widely used for this purpose but would like to avoid this route if possible
mannitol has some efficacy but getting stuff across the bbb is really tough
There is a new way to disrupt the BBB temporally with ultrasounds to treat animals with compounds that do not cross the BBB, and even cells, This paper uses this approach (PMID: 22114718) I was wondering if you could prevent the BBB disruption with your compound.
You may want to try LPS (Lipopolysaccharide). Please see for example -
http://www.ncbi.nlm.nih.gov/pubmed/25268765
Mannitol or other hyperosmotic solutions into the carotic artery works well, but just for a very short time. You can try systemic inflammation with LPS or TNFa but you will have side effects throughout the body! I guess there is no other way to proof your component by inducing a pathologic condition i.e. stroke (MCAO), TBI, SAB, brain tumor... You may open the BBB from the other side by injecting inflammatory or hyperosmolaric solutions or tumor cells directly through the skull into the parenchyma! This would affect only a small region were you can evaluate the leakage by MRI for example!
Thank you to everyone for the input. This is just a pilot so I think we are going to try LPS first and see what happens. All great suggestions and I appreciate the guidance
- Badges
- Science topic
- Similar topics
- Medicine
- Disease
- Disease Models
- Animal Models
- Rodent Models