Date(s) - 03/28/2012
2:00 pm - 4:00 pm
Neural stem/progenitor cell research is on the cusp of achieving real strategies for central nervous system repair. Recent studies provide evidence that grafts can survive, functionally integrate, and ultimately augment damaged neural networks. However, understanding the impact of functional integration on existing brain circuitry is an understudied area of research. This dissertation employs microelectrode arrays (MEAs), which facilitate real-time optical and electrophysiological data collection across entire neural networks, to first determine the faculty for adult hippocampal neural progenitor cell (NPC) derivatives to produce spontaneous action potentials and network bursts when cultured alone, and then to investigate the effects of adult NPC addition to intact or damaged primary neural networks. MEA-plated primary cultures transition through high frequency “superbursting” that is ultimately refined into mature, regular burst patterns. When plated alone, adult NPC-progeny fail to establish synchronized bursting that primary and embryonic stem cell-derived cultures readily form. However, NPCs evoke re-emergent superbursting in primary neural cultures. Developmental superbursting is thought to accompany heightened plasticity both in culture preparations, and across brain regions. This work also uses online MEA recordings to show activity degradation during hypoxia-ischemia via oxygen-glucose deprivation (OGD), and investigate the ability of subsequent NPC addition to protect or restore network activity. Spike rates initially rise during the first 5min of OGD due to increased asynchronous activity between bursts. Action potentials decrease in amplitude, and all activity ultimately ceases by ~16min. Spontaneous activity recovers following reperfusion after 20min-OGD, but little recovery is observed after longer durations. Shorter duration OGD may effectively model the silenced circuits found in the penumbra of a stroke while longer OGD might effectively model the dying circuits found in the core. NPC addition 24hrs following 3hr-OGD increases low-level proliferation, and decreases cell death, preferentially protecting mature neurons from oxidative stress and death for at least a week after OGD exposure. Although co-culture in OGD-compromised primary cultures did not affect NPC behavior, NPCs partially rescued network activity. The MEA co-culture model established in this dissertation is an effective bioassay for examining the effects of potential neuroregenerative therapies on existing network activity, before these strategies are translated in vivo.