Current Approaches to Monitor Macromolecules Directly from the Cerebral Interstitial Fluid

Gaining insights into the pharmacokinetic and pharmacodynamic properties of lead compounds is crucial during drug development processes. When it comes to the treatment of brain diseases, collecting information at the site of action is challenging. There are only a few techniques available that allow for the direct sampling from the cerebral interstitial space. This review concerns the applicability of microdialysis and other approaches, such as cerebral open flow microperfusion and electrochemical biosensors, to monitor macromolecules (neuropeptides, proteins, ... ) in the brain. Microdialysis and cerebral open flow microperfusion can also be used to locally apply molecules at the same time at the site of sampling. Innovations in the field are discussed, together with the pitfalls. Moreover, the ‘nuts and bolts’ of the techniques and the current research gaps are addressed. The implementation of these techniques could help to improve drug development of brain-targeted drugs.