Migration of monocytes after intracerebral injection at entorhinal cortex lesion site

Abstract

The lack of classical lymph vessels within brain tissue complicates immune surveillance of the CNS, and therefore, cellular emigration out of the CNS parenchyma requires alternate pathways. Whereas invasion of blood-derived mononuclear cells and their transformation into ramified, microglia-like cells in areas of axonal degeneration across an intact BBB have been demonstrated, it still remained unclear whether these cells reside permanently, undergo apoptosis, or leave the brain to present antigen in lymphoid organs. With the use of ECL of mice and injection of GFP-expressing monocytes, we followed the appearance of injected cells in spleen and LNs and the migratory pathways in whole-head histological sections. Monocytes migrated from the lesion site to deep CLNs, peaking in number at Day 7, but they were virtually absent in spleen and in superficial CLNs and inguinal LNs until Day 21 after lesion/injection. In whole-head sections, GFP monocytes were found attached to the olfactory nerves and located within the nasal mucosa at 48 hpi. Thus, monocytes are capable of migrating from lesioned brain areas to deep CLNs and use the cribriform plate as an exit route.

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…While some studies have followed injections of T cells, monocytes, or dendritic cells from the brain parenchyma to their ultimate drainage into the cervical lymph nodes, others have failed to document any such drainage after intracerebral injection (79,(86)(87)(88)(89). Furthermore, the perivascular pathway is likely incapable of allowing the passage of immune cells (48), raising the possibility that at least some of the observed drainage might be due to postinjection leakage into the CSF/meningeal compartment.…”

“…Furthermore, the perivascular pathway is likely incapable of allowing the passage of immune cells (48), raising the possibility that at least some of the observed drainage might be due to postinjection leakage into the CSF/meningeal compartment. In yet other studies, the cribriform plate was proposed as the route by which immune cells exit the CNS and reach the nasal lymphatics (87,88). Clearly, the notion that T cells or dendritic cells within the brain parenchyma have migratory potential to leave the parenchyma remains a matter of debate.…”

“…Macromolecules and tracers injected into the SAS rapidly reach the cervical lymph nodes, suggesting that CSF constituents can easily drain outside the CNS and thus potentially elicit an immune response. The different routes potentially implicated in such drainage were described earlier (see "Dural ers entering the lymphatic vessels of nasal mucous membranes through the cribriform plate suggested that the most important CSF outflow mechanism into extracranial lymphatic system would be via perineural SAS enveloping the olfactory nerve sheaths (47,(61)(62)(63). Besides cranial perineural flow, tracer studies also suggested that CSF from the spinal SAS would terminate in the regional lymphatics outside of the spinal canal via perineural pathways (64,65).…”

Le drainage lymphatique cérébral

“…Ainsi, puisque le SNC apparaissait dépourvu de système lymphatique, la seule voie utilisable par les cellules immunitaires était la voie de la plaque cribriforme. Par cette voie, les cellules immunitaires devaient sortir du SNC et rejoindre le réseau lymphatique de la muqueuse nasale puis les ganglions [8,9]. Cependant, des travaux récents ont conduit à l'observation d'un réseau lymphatique conventionnel et fonctionnel au sein même du SNC [10][11][12], confirmant des hypothèses et des observations réalisées auparavant mais ignorées de la communauté scientifique.…”

Editorial: Route by which monocytes leave the brain is revealed

“…In this issue, Kaminski et al [9] shed new light on the traffic of monocytes from the brain to deep CLNs. The central claim of the study is that monocytes injected into a traumatic lesion in the mouse brain subsequently reach the deep CLNs via the cribriform plate.…”