RT Journal Article
SR Electronic
T1 Meningeal lymphangiogenesis and enhanced glymphatic activity in mice with chronically implanted EEG electrodes
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2223-19
DO 10.1523/JNEUROSCI.2223-19.2020
A1 Natalie L. Hauglund
A1 Peter Kusk
A1 Birgitte R. Kornum
A1 Maiken Nedergaard
YR 2020
UL http://www.jneurosci.org/content/early/2020/02/10/JNEUROSCI.2223-19.2020.abstract
AB Chronic electroencephalography (EEG) is a widely used tool for monitoring cortical electrical activity in experimental animals. While chronic implants allow for high-quality, long-term recordings in preclinical studies, the electrodes are foreign objects and might therefore be expected to induce a local inflammatory response. We here analyzed the effects of chronic cranial electrode implantation on glymphatic fluid transport and in provoking structural changes in the meninges and cerebral cortex of male and female mice. Immunohistochemical analysis of brain tissue and dura revealed reactive gliosis in the cortex underlying the electrodes and extensive meningeal lymphangiogenesis in the surrounding dura. Meningeal lymphangiogenesis was also evident in mice prepared with the commonly used chronic cranial window. Glymphatic influx of a cerebrospinal fluid tracer was significantly enhanced at 30 days post-surgery in both awake and ketamine-xylazine anesthetized mice with electrodes, supporting the concept that glymphatic influx and intracranial lymphatic drainage are interconnected. Altogether, the experimental results provide clear evidence that chronic implantation of EEG electrodes is associated with significant changes in the brain's fluid transport system. Future studies involving EEG recordings and chronic cranial windows must consider the physiological consequences of cranial implants, which include glial scarring, meningeal lymphangiogenesis and increased glymphatic activity.Significance statement: This study shows that implantation of extradural electrodes provokes meningeal lymphangiogenesis, enhanced glymphatic influx of cerebrospinal fluid, and reactive gliosis. The analysis based on CSF tracer injection in combination with immunohistochemistry showed that chronically implanted electroencephalography (EEG) electrodes were surrounded by lymphatic sprouts originating from lymphatic vasculature along the dural sinuses and the middle meningeal artery. Likewise, chronic cranial windows provoked lymphatic sporuting. Tracer influx assessed in coronal slices was increased in agreement with previous reports identifying a close association between glymphatic activity and the meningeal lymphatic vasculature. Lymphangiogenesis in the meninges and altered glymphatic fluid transport after electrode implantation have not previously been described and adds new insights to the foreign body response of the central nervous system.