Microalgae-based photosynthetic strategy for oxygenating avascularised mouse brain tissue - An in vitro proof of concept study.

Hypoxic brain injury is a leading cause of loss of quality of life globally for which there are currently no effective treatments. There has been increasing interest in incorporating photosynthesising agents into hypoxic tissue as a mechanism for in situ oxygen delivery, independent of vascular perfusion. To date this has not been tested in the brain. The oxygen production capacity of Chlamydomonas reinhardtii microalgal cultures was measured in artificial cerebrospinal fluid (aCSF) in benchtop assays and in cortical slices in situ. Cortical slice function was quantified by measuring the length, frequency and amplitude of seizure-like event (SLE) activity - in conventionally oxygenated aCSF, C. reinhardtii cultures, unoxygenated and deoxygenated aCSF. The possibility of direct toxic algal effects was investigated by exposing slices to cultures for 5 h. An oxygen level of 25 mg.L was achieved with C. reinhardtii in no-Mg aCSF. Slice SLE function was preserved in C. reinhardtii, without the need for supplemental oxygen. In contrast, functional parameters deteriorated in unoxygenated and deoxygenated aCSF. In the former, there was a 66% reduction in SLE frequency and a 37% reduction in event amplitude. In the latter, SLE activity ceased completely. No toxic algae effects were seen in slices exposed to cultures for 5 h. These results confirm that C. reinhardtii oxygenation of aCSF can sustain cortical network activity - without tissue toxicity for the normal lifespan of an acute cortical slice. This study shows promise for the concept of photosynthesis as a mechanism for providing oxygen to rescue ischaemic avascularised brain tissue.