During the project a significant number of important techniques was set up, including electroencephalogram of awake and anesthetized rodents and microdialysis of small-molecule drugs from the brain parenchyma. An especially important and novel line of work included the combination of single-photon emission tomography (SPECT) and magnetic resonance imaging (MRI) of small molecule drugs and large biological molecules to track the flow of cerebrospinal fluid either in the head and neck area or the whole animal.
We found that the SPECT imaging can provide quantitative data about the influx of cerebrospinal fluid in the brain but also map the different efflux routes of cerebrospinal fluid from the intracranial space. The resolution of SPECT is poorer than MRI imaging, but on the other hand the whole animal can be covered quantitatively. We found that the anesthetic state per se is not enough to induce high glymphatic state and efficient glymphatic delivery of drugs from the cerebrospinal fluid space, instead, several other physiological factors govern glymphatic flow. We found the manipulation of plasma osmolarity to be a highly relevant method for enhancing glymphatic flow and delivering drugs from the cerebrospinal fluid to the brain.
Part of the results obtained are published in international journals as peer-reviewed articles. So far, one articles are already published, one review article has been submitted to a high-profile journal and four more are in preparation. Two collaborative papers (related to the project, but not included as main scientific output) and one article directed to physicians (in Finnish) are published as well. In addition, results have been presented at international conferences, and also in several smaller clinic meetings. In addition, the glymphatic system and its implications were presented in several press interviews.
The project did not yield specific intellectual property. However, benefits for the research community, achieved through presentations of results at local meetings and international conferences, include the important consideration for the field that the glymphatic system holds potential in the delivery of drugs to the brain in preclinical models. The next step in this line of research is aiming at more thorough understanding of the physiological factors governing glymphatic flow, but also studying concepts of glymphatic drug delivery in clinical trials.
