Clinical Status of Neuroprotection in Cerebral Ischemia

Introduction

Cerebral ischemia, resulting in neuronal death, is seen in a wide range of conditions. Most often, it results from arterial occlusion secondary to thromboembolic or atherosclerotic diseases. Trauma is also a common cause of ischemic disease. In other instances, it can be iatrogenic in the setting of interventional treatments, such as those for carotid artery stenosis or cerebral aneurysms. Neuroprotective strategies in clinical practice fall into one of the three categories: to prevent disruption of ion homeostasis in the neurovascular unit before reaching ischemic threshold, to salvage at-risk territory (ischemic penumbra), and to prevent secondary injury in normal brain tissue near ischemia-related cerebral edema. In this chapter, we review these categories and their roles in the current clinical practice.

Primary Stroke Prevention During Interventions

Although stroke (cerebral ischemia) is most commonly a pathological and unexpected event, there are certain instances when certain therapeutic interventions temporarily limit blood flow to brain tissue, thereby placing the involved territory at risk for injury. An example of such instance is during carotid endarterectomy, when clamping of the common carotid artery temporarily arrests blood flow to the distal internal carotid artery. Another example is during brain aneurysm surgery, when on occasion, a segment of the parent vessel may be temporarily occluded to facilitate final dissection and clipping of the aneurysm. During any of these instances, the amount of time the blood vessels can be occluded without resulting in stroke is highly variable. It appears to be dependent on many patient-specific factors, such as collateral circulation from other vascular territories, although the variability in maximally tolerated ischemia time from patient to patient is not well understood. Patients under general anesthesia are often closely monitored with somatosensory evoked potentials and motor evoked potentials to detect the onset of early ischemic changes. Measures to augment blood flow through collateral circulation, including systemic hypertension, are thought to be helpful and are routinely used in clinical practice .

Alternative strategies to maximize the ischemia interval are centered on decreasing cerebral metabolic demand. Studies have examined the use of mild hypothermia , although this was not found to be beneficial in patients undergoing surgery for ruptured brain aneurysms. Its potential benefit in patients undergoing elective procedures, or more specifically in those undergoing temporary occlusion of cerebral arteries, is not well studied. Another technique frequently used to decrease cerebral metabolic demand is anesthetic-induced electroencephalographic (EEG) burst suppression. Burst suppression is an EEG pattern in which high-voltage activity alternates with isoelectric quiescence. It is characteristic of an inactivated brain, is seen with deep levels of general anesthesia, and is thought be associated with a decrease in cerebral metabolic rate coupled with the stabilizing properties of ATP-gated potassium channels . In clinical practice, to achieve 100% intensity burst suppression, the rate of infusion of an anesthetic (typically propofol) can be manipulated based on real-time feedback from EEG monitoring. The neuroprotective benefit of this technique to extend the ischemic window is a subject of ongoing investigation.