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loss-and-recovery-of-functional-connectivity-in-cultured-cortical-networks-exposed-to-hypoxia.ris

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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. Besides activity recovery, return of brain functioning requires restoration of connectivity. However, low activity has been shown to initiate compensatory mechanisms that affect network connectivity. We investigated the effect of transient hypoxia and compensatory mechanisms on activity and functional connectivity using cultured cortical networks on multi-electrode arrays. Networks were exposed to hypoxia of controlled depth (10%-90% of normoxia) and duration (6-48h). First, we determined how hypoxic depth and duration govern activity recovery. Then, we investigated connectivity changes during and after hypoxic incidents, mild enough for activity to recover. Shortly after hypoxia onset, activity and connectivity decreased. Following 4-6h of ongoing hypoxia, we observed partial recovery. Only if the hypoxic burden was limited, connectivity showed further recovery upon return to normoxia. Partial recovery during hypoxia was dominated by restored baseline connections, rather than newly formed ones. Baseline strengths of surviving (persisting or recovered) and lost connections did not differ, nor did baseline activity of their presynaptic neurons. However, postsynaptic neurons of surviving connections were significantly more active during baseline than those of lost connections. This implies that recovery during hypoxia reflects an effective mechanism to restore network activity, which not necessarily conserves pre-hypoxia connectivity. Read more↗

Size2.21KB
Content typeapplication/x-research-info-systems
Updated1 year ago
Checked1 year ago
Hostjn.physiology.org
Keywordsloss and recovery functional connectivity cultured cortical networks exposed hypoxia ris
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