Cerebral ischemia results when the metabolic demands of cerebral tissue exceed substrate (primarily O₂) delivery. Ischemia can be categorized as either global—with interruption of substrate delivery to the entire brain, as occurs in cardiac arrest—or focal—with interruption of substrate delivery to a defined region of the brain, such as is produced by embolic cerebral artery occlusion. Cerebral protection is an attempt to prolong the ischemic tolerance of brain tissue and to reduce or abolish neuronal injury.

The traditional concept of cerebral metabolism is illustrated in Figure 131-1. Cerebral metabolism may be divided into a functional component and a cellular integrity component. The functional component comprises 60% of neuronal O₂ use. This component is responsible for generating action potentials and may be assessed by evaluating the electroencephalogram. The cellular integrity component consists of the remaining 40% of O₂ utilized for protein synthesis and other activities geared toward maintaining cellular integrity.

Anesthetic agents and hypothermia are both capable of reducing the functional component of cerebral metabolism, resulting in, at most, a 60% reduction in O₂ use. Hypothermia, however, can further reduce O₂ use by also decreasing the cellular integrity component. In this traditional and simplistic O₂ supply–metabolic demand paradigm, cerebral protection may be produced by simply altering the balance in favor of supply by increasing cerebral perfusion pressure (CPP) and O₂ delivery while depressing cerebral metabolism via anesthetic agents and hypothermia.

New evidence paints a much more complex picture of cerebral ischemia, in which an initial ischemic event may trigger a process of neuronal demise that continues long after the inciting event has resolved (Figure 131-2). Excitotoxicity is a cascade of glutamate-mediated neuronal demise that occurs shortly after the onset of neuronal ischemia. Apoptosis (programmed cell death via proteases) and inflammation are initiated by the ischemic event and continue to contribute to neuronal death for days. In this newer model of cerebral ischemia, it may be possible to limit ischemic damage by invoking cerebral protective therapies before, during, or after an ischemic event (Table 131-1). The currently available evidence in support of the use of cerebral protection is derived from a mixture of human experiments and animal data extrapolated to human subjects.