LOSS AND RECOVERY OF CONNECTIVITY IN AN IN VITRO MODEL OF THE ISCHEMIC PENUMBRA
Abstract
In the core of a brain infarct, loss of neuronal function is followed by neuronal death within minutes. In an area surrounding the core (penumbra), some perfusion remains. Here, neurons initially remain structurally intact, but massive synaptic failure strongly reduces neural activity. Activity in the penumbra may eventually recover or further deteriorate towards massive cell death, but factors that determine either outcome remain unclear.
We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Activity and connectivity strongly decreased during hypoxia, and recovered upon return to normoxia if the hypoxic burden was sufficiently mild. Stimulus responses suggested that decreased activity and connectivity resulted from failing synapses, which was confirmed by FM-1 staining. Neurons initially remained intact during hypoxia.
Early during hypoxia-induced low activity, we observed partial recovery of activity and connectivity, possibly reflecting compensatory synaptic enhancement. Particularly connections with the most active post synaptic neurons were restored, supporting the hypothesis that recovery during hypoxia reflects an effective mechanism to restore network activity.
This partial recovery persisted for up to ~20 hours, seemingly independent of the remaining amount of oxygen. If the oxygen supply was not restored within this period, damage became irreversible, eventually leading to massive cell death. These findings suggest that insufficient activity may eventually lead to neuronal death, even if the remaining oxygen is in principle sufficient for neurons to survive.
Wednesday 8 March 2017, 16:30 - 17:30 h
Building Carré - room CR 3.178