Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain

Brain perivascular macrophages (PVMs) belong to border-associated macrophages. PVMs are situated along blood vessels in the Virchow-Robin space and are thus found at a unique anatomical position between the endothelium and the parenchyma. Owing to their location and phagocytic capabilities, PVMs are regarded as important components that regulate various aspects of brain physiology in health and pathophysiological states. Here, used LYVE-1 to identify PVMs in the mouse brain. We used brain-tissue sections and cleared whole-brain to learn how they are distributed within the brain and across different developmental postnatal stages. We find that LYVE-1+ PVMs associate with the vasculature in a brain-region-dependent manner, where the hippocampus shows the highest density of LYVE-1+ PVMs. We show that their postnatal distribution is developmentally dynamic and peaks at P10-P20 depending on the brain region. We further demonstrate that their density is reduced in the APP/PS1 mouse model of Alzheimers Disease. In conclusion, our results show an unexpected heterogeneity and dynamics of LYVE-1+ PVMs, and support an important role for this population of PVMs during development and in regulating brain functions in steady-state and disease conditions.

Controversies and Misconceptions Related to Cerebrospinal Fluid Circulation: A Review of the Literature from the Historical Pioneers’ Theories to Current Models

Models of cerebrospinal fluid (CSF) circulation have been mainly proposed in the last century: CSF goes from the ventricles to the subarachnoidal space (SAS), passing through the aqueduct and the foramen of Luschka and Magendie. Indeed, new models, involving the Virchow-Robin space (VRS) and the perivascular space (PVS), have been proposed. We critically reviewed the literature, in order to clarify the “classical” errors and to discuss the “new” models that are evolving currently. Conclusions of past experiments are often not justified, due to lack of reproducibility and methodological issues. On the other hand, investigation on the microanatomy of Virchow-Robin spaces (VRS) and several new experiments showed a potential pathway for a more complex CSF “circulation,” with chaotic and unpredictable flows. It seems reasonable to elaborate a new model of CSF physiology, including new findings and questioning old certainties. However, proved data are still missing and it is hazardous to come to final conclusions. More studies are needed.

Dilated Virchow-Robin Space and Dopamine Transporter Imaging in the Striatum of Patients with Parkinsonism

Objective: The radiological and clinical significance of a dilated Virchow-Robin space (dVRS) in the striatum (STR) remains unclear. We investigated the role of dVRS in STR on parkinsonism and dopamine transporter positron emission tomography (DaT-PET) findings. Methods: Patients with parkinsonism who underwent both brain magnetic resonance imaging and DaT-PET were included. Clinical status was evaluated by Hoehn and Yahr (HY) stage, Korean-Mini Mental Status Examination (K-MMSE), Montreal Cognitive Assessment Korea (MoCA-K), and Frontal Assessment Battery (FAB). dVRS was assessed by semi-quantitative and quantitative scales in each of the three segments of STR (caudate nuclei, anterior and posterior putamen) and was expressed as a dVRS score. DaT-PET was qualitatively assessed as either normal or abnormal in each segment. The relationship between dVRS and DaT-PET abnormality (ab-DaT-PET) was designated in each segment as either concordant or discordant. A concordant segment was defined by the presence of dVRS with ab-DaT-PET [Concordance rate (CR)=number of concordant segments/number of concordant and discordant segments]. Results: Eleven patients were included. There was no significant correlation between the presence of dVRS and ab-DaT-PET. The mean CR was 0.39. CR was not significantly correlated with any clinical or neuroimaging scales. The dVRS score was significantly correlated with K-MMSE, MoCA-K, and FAB (r=−0.675, −0.847, and −0.868, respectively) but not with HY stage. Conclusion: dVRS in STR played no significant role on dopaminergic innervation revealed by DaT-PET and made little contribution to clinical parkinsonism; however, it was correlated with cognitive impairment.