Functional effects of haemoglobin can be rescued by haptoglobin in an in vitro model of subarachnoid haemorrhage

Subarachnoid haemorrhage causes significant cognitive and functional disability in survivors, and one contributing factor is exposure of neurons to haemoglobin causing cell loss and dysfunction. In this in vitro subarachnoid haemorrhage model, haemolysate application to cultured neurons impairs cytoskeletal integrity. Furthermore, amplitude of AMPA receptor-mediated synaptic currents is reduced by haemolysate, driven by reduction in GluA1 expression. These deficits can be prevented with application of exogenous haptoglobin without off-target effects. These results provide new insight into neuronal dysfunction in haemorrhagic stroke and add support for haptoglobin as a novel therapeutic for reducing brain damage after subarachnoid haemorrhage. AbstractDuring subarachnoid haemorrhage, a blood clot forms in the subarachnoid space releasing extracellular haemoglobin (Hb), which causes oxidative damage and cell death in surrounding tissues. High rates of disability and cognitive decline in SAH survivors are attributed to loss of neurons and functional connections during secondary brain injury. Haptoglobin sequesters Hb for clearance, but this scavenging system is overwhelmed after a haemorrhage. Whilst exogenous haptoglobin application can attenuate cytotoxicity of Hb in vitro and in vivo, the functional effects of sub-lethal Hb concentrations on surviving neurons and whether cellular function can be protected with haptoglobin treatment remain unclear. Here we use cultured neurons...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research