Towards a dynamical network view of brain ischemia and reperfusion. Part IV: additional considerations

The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the fourth in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. Here we consider additional issues to round out and close out this initial presentation of the bistable network view of brain ischemia. Initial considerations of the network architecture underlying the post-ischemic state space are discussed. Network and differential equation models of brain ischemia are compared. We offer a first look at applying the bistable model to focal cerebral ischemia. The limitations of the present formulation of the bistable model are discussed. This work concludes with a series of questions by which to direct future efforts.