PK/PD in the Brain
The blood-brain barrier (BBB) is a natural shield protecting the brain. It regulates the exchange of nutrients, metabolites and chemical messengers between the blood and brain. The BBB also prevents harmful substances from entering and damaging the brain. This highly effective barrier, however, can also prevent potentially neuroactive substances from reaching appropriate targets. For researchers developing neuroactive drugs, therefore, it is of great interest to know whether and to what extent an active pharmaceutical component can penetrate the BBB.
- The use of cerebral open flow microperfusion technology (cOFM ) allows us to take a look behind the BBB and assess concentrations and effects of neuroactive substances directly in the targeted brain tissue.
- We can conduct continuous PK monitoring in brain tissue. Our experiments have shown that the BBB has fully healed and is reestablished 15 days after the implantation of the cOFM probe in the brain. The cOFM probe has been specially designed to avoid reopening of the BBB or causing additional trauma to the brain after implantation. cOFM allows continuous sampling of interstitional fluid with the BBB intact.
- cOFM allows continuous monitoring of BBB integrity while simultaneously measuring biomarkers and pharmaceuticals.
- cOFM enables daily, time-resolved measurements over several days. This reduces the overall number of test subjects required.
- cOFM can save time and money because the suitability of a neuroactive substance can already be determined at an early (preclinical) stage of drug development.
Materials and Methods
- OFM probe from PEEK material: 0.5 mm diameter, variable length (variable)
- High-precision stereotactic implantation
- Probe with a healing dummy allows the rapid regeneration of tissue after implantation
- No additional opening of the BBB or trauma to the brain tissue after initial implantation
- No tissue in-growth into the guide cannula
- Patent pending