REVERSIBILITY OF FUNCTIONAL CONNECTIVITY LOSS AFTER TRANSIENT MILD HYPOXIA OF VARYING DEGREE AND DURATION
Stroke is very common in western countries, and can lead to cognitive impairment or death. The absence of oxygen in the infarct core quickly leads to cell death. Remaining but limited perfusion in the region around the core (the penumbra) causes energy depletion in neurons, and disrupts synaptic transmission and thus connectivity. Connectivity loss probably correlates with loss of cognition and restoration of connectivity seems crucial for possible treatment. However, in vivo, connectivity is difficult to assess due to limited access to the neurons and restricted experimental freedom.
We studied the effects of hypoxia on functional connectivity in cultured neuronal networks on a multi-electrode array under varying degrees and durations of hypoxia. Connectivity was estimated with conditional firing probability analysis. Several electrodes were stimulated throughout the experiment to obtain a measure for synaptic functioning.
The first six hours of hypoxia resulted in reduced activity and connectivity, followed by restoration of activity and functional connectivity to baseline values upon re-oxygenation. Under persisting hypoxic conditions, after 6 hours some recovery occurred as observed by increased activity and connectivity, until approximately 24 hours. Cultures that survived 24 hours of severe hypoxia, showed permanently decreased activity and reduced functional connectivity. If severe hypoxia was maintained even longer, both activity and connectivity further dropped, and were irreversibly lost. In cultures that survived 48 hours of hypoxia, mean connectivity strength tended to remain around baseline values, though several individual connections were lost in the process. We found no significant difference between the baseline connectivity strength of surviving and lost connections, suggesting that protective mechanisms do not prefer weaker or stronger connections. The formation of new connections during hypoxia occurred at comparable rates as in normoxic control experiments, and suggests that the mechanism for recovery through new connections are limited.
Wednesday 27 January 2016, 14:30 h
Building Carré - room CR 3.022