Glial influences on neuron survival and regeneration in the CNS environment

Abstract

Inflammation plays important role in limiting neuronal survival and axonal regeneration. Meanwhile, microglia and astrocytes are key players in mediating inflammation in CNS. Controlling inflammation thus is a crucial step in promoting neural survival and axonal regeneration. In our recent experiments, we have established an in vitro model to study inflammatory response in the CNS after ischemic (glucose and oxygen deprived)/hypoxic (oxygen deprived) injury. Methods: E-16 cortical neurons from rats were seeded on ischemic/hypoxic-injured glial cells, isolated from 1-day old rat brains, and co-cultured for 7 days. Using MAP2 immunocytochemistry, neuronal survival and neurite outgrowth were assessed by cell counts and image analysis (Neurolucider). Results: Our data suggest that small amount of inflammation (0.5 hr of ischemic treatment on glial cells) promotes neuronal survival and neurite extension. However, in longer ischemic/hypoxic-treated groups (>2hrs), both neuronal survival and neurite extension were decreased. Neurotrophic factors (NTF) are believed to modulate microglia, and glial cells have been known to release NTFs. However, detail mechanism on the regulation of NTFs by glial cells has not been fully understood. Our hypothesis is that the release of cytokines from the glial cells as a response to inflammation will decrease NTFs release, which leads to a decrease of neuronal survival and neurite extension. This abstract is sponsored by The Hong Kong Society of Neuroscience. Supported by the Hong Kong Regional Grant Council and The University of Hong Kong.