The role of glia in the blood-brain barrier integrity

The blood-brain barrier (BBB) is an extremely selective structure sharing dynamic interactions both with neurons and glial cells, thus directly contributing to the formation of the neuro-vascular unit (NVU). The NVU term was leap out more than 20 years ago highlighting the close relationship between brain cells and cerebral vessels. The complexity of the NVU is mainly due to the interconnection and the mutual influence of the single cellular compartment and, among the plethora of different kind of cells, glial cells play a pivotal role in maintain the physiological brain homeostasis, together with the contribution for the BBB formation. On the other hand, the glial compartment alteration, has been demonstrated to indirectly affect the brain cells. The aim of this study is to better understand the mechanisms underlying the alterations of the BBB, the first structure involved against toxic insult, as well as the role of glial cells, the primum movens in neurodegenerative disorders. Cell viability, oxidative stress marker as well as glial activation marker was evaluated both during physiological and toxic condition, such as the presence of cadmium acetate, at different concentration (1-10 μM), on astrocyte and microglial cell lines alone (DITNC1 and BV-2, respectively), or in co-culture with rat brain endothelial cells (RBE4). Our preliminary data indicate that, during physiological condition, astrocytes seems to reinforce the BBB integrity increasing the brain endothelial cells viability and better localizing the claudin 5 tight junction. On the other hand, microglial cells do not alter the brain endothelial cells viability during co-culture condition, in comparison to monoculture (RBE4 alone). Moreover, during cadmium acetate toxic insult, the presence of astrocytes in co-culture lend a better protection to RBE4 cells, in comparison to microglial cells. The microglia-dependent lack of protection might be explained by a more sensitivity to oxidative stress during toxic stimulation, especially at lower times (4 hours). In conclusion, these preliminary data on glial cells behavior on BBB preservation and alteration underline the main role of astrocytes in reinforcing and preventing the brain endothelial cells dysregulation. However, once microglial cells are damaged, this deleterious effect dramatically reflects on BBB integrity.