Events

ACYLATED GHRELIN IMPROVES NEURONAL RECOVERY IN HYPOXIA-INDUCED SYNAPTIC FAILURE IN RAT DISSOCIATED CORTICAL NEURONS

Abstract

In the core of a brain infarct, loss of neuronal function is followed by neuronal death within minutes. In the penumbra, surrounding the infarct core, damage is not yet irreversible due to some blood supply from surrounding arteries. It is assumed that in the penumbra neurons are inactive, but structurally intact and viable. They may eventually recover, or proceed to cell death, depending on remaining levels of perfusion and timely reperfusion. Therapies to prevent collateral damage of penumbral brain tissue have a large potential to improve neurological outcome of patients with ischemic stroke, but are lacking. Therefore, we developed an in vitro model using dissociated cortical neurons to investigate neuronal dynamics during and after partial hypoxia. Briefly, we applied hypoxia (PO2 lowered from 150 to 21 mmHg) during 6h in 104 cultures. Three hours after restoration of normoxia, half of the cultures were treated with ghrelin for 24h. Cultures with and without ghrelin treatment were processed immunocytochemically for detection of the synaptic marker synaptophysin. Additionally, the fraction of the inactive synapses was evaluated by staining for the marker synapsin-1. We observed that hypoxia led to drastic decline of the number of synapses, followed by some recovery after return to normoxia, but still below the pre-hypoxic level. Ghrelin treatment significantly increased the synaptic density, as compared with controls or with the pre-hypoxic period. Furthermore, ghrelin treated cultures had much less inactive synapses than the non-treated group, and the ratio of active/inactive synapses was close to the pre-hypoxic level. In conclusion, ghrelin may improve synaptic recovery after partial hypoxia, such as present in the penumbra.


Keywords: brain hypoxia, stroke, penumbra, synaptic activity, ghrelin, synaptic recovery


Wednesday 27 May 2015, 16:30 - 17:30 h

Building Carré - room CR 3.718