Article
Migration of monocytes in lesioned mice after intracerebral injection
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Published: | April 28, 2011 |
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Objective: After traumatic brain injury, cellular emigration out of the central nervous system (CNS) is either impossible or requires alternative pathways, in light of the lack of classical lymph vessels within brain tissue. While invasion of blood-derived mononuclear cells and their transformation into ramified microglia-like cells in areas of axonal degeneration has been demonstrated, it is still unclear whether these cells reside permanently, undergo apoptosis, or leave the brain to present antigen in lymphoid organs after lesion or injury.
Methods: Entorhinal cortex lesion was performed on adult wild-type C57BL/6 mice and monocytes were isolated from mice expressing green fluorescent protein (GFP) under the ß-actin promotor. Following injection, animals were allowed to survive from a few minutes to 21 days. Whole head/neck sections were analyzed, as well as isolated brains, lymph nodes and spleen.
Results: We were able to follow the appearance of injected GFP cells in spleen and lymph nodes and the migratory pathways in whole-head histological sections. Monocytes migrated from the lesion site to deep cervical lymph nodes (CLN) with a peak in numbers at day 7, but they were virtually absent from spleen as well as in superficial cervical and inguinal lymph nodes at least until day 21 after lesion and injection. At 48 hours post-lesion, the injected GFP cells were found in the cribriform plate, directly proximal to the olfactorial nerve, at the point at which it penetrates the lamina cribosa in a caudal direction towards the sinus, coming from the olfactory bulbus. Thus, monocytes are capable of migrating from lesioned brain areas to deep CLN using the first cranial nerve as an exit route.
Conclusions: Infiltrating monocytes to a central lesion site deriving from blood monocytes are considered to play a crucial role after CNS injuries. The discovery of the leukocyte-trafficking afferent from the CNS demonstrates the critical role blood-derived cells play in post-lesional deregulation and regeneration. Our finding that monocytic cells migrate to peripheral lymph nodes demonstrates that immune cell activity does not necessarily take place inside the brain. Therefore, therapeutic strategies against central impairment should be targeted to peripheral events. This would circumvent brain tissue, which is advantageous because as the CNS possesses limited regenerative capacity, it is invariably susceptible to damage mediated by inflammation.