It has become evident mainly from experimental work that permanent and transient depolarisations of gray matter of the central nervous system may be major causes of progressive deterioration in border zones of traumatic or ischemic foci. They appear to accompany or possibly cause clinical deterioration (as is frequently observed in patients with these conditions). These depolarisations, referred to as peri-infarct depolarisations (PID) have attracted interest over the past two or more decades among scientists in the field. They resemble another phenomenon, cortical spreading depression (CSD) (Leão, 1944), a wave of mass neuronal and glial depolarisation, which propagates through grey matter in the central nervous system in response to a pathologic stimulus, at a velocity of 1 and 5 mm per minute. Grafstein (1956) showed that (1) there is brief and intense neuronal firing at onset of the depolarization, and (2) that recovery is energy and perfusion-dependent; she also suggested that release of potassium ions might contribute to the propagation. CSD can be elicited in experimental animals by chemical, electrical, and mechanical stimuli, with varying degrees of ease. CSD provoked in healthy, normally perfused neural tissue does not induce persistent metabolic stress or cellular damage, and indeed such induction of CSD in animal experiments may confer protection against the adverse effects of a subsequent ischaemic insult (Kobayashi et al., 1995). Lauritzen (1994) argued persuasively for CSD as the basis of migraine with aura, and this suggestion was later supported by results of fMRI studies in a migraineur (Hadjikhani et al, 2001).
In animal models of focal cerebral ischaemia, usually induced by occlusion of the middle cerebral artery, PIDs occur around the periphery of the core territory, with electrophysiological features essentially identical with CSD, and similar capacity to propagate across cerebral cortex. These events are associated with infarct expansion, or recruitment of at-risk cortical territory into the expanding core, and have been shown capable of causing this expansion, in the absence of therapeutic intervention. Indeed it has been hypothesized that glutamate release may be involved in PID generation, and that excitotoxicity may accomplish detrimental effects via this route (Hossmann, 1994; Obrenovitch and Urenjak, 1997). Some experimental neuro-protection treatments for stroke act to decrease the incidence of PID (Iijima et al., 1992; Chen et al. 1993; Busch et al., 1996).
In traumatic and ischaemic (especially in middle cerebral artery occlusion and aneurysmal subarachnoid haemorrhage) brain injury in humans, a phase of delayed deterioration often associated with severe and refractory brain swelling develops between 2 and 5 days after the initial ictus, and is associated with poor or fatal outcome. The cause and mechanism of this deterioration remain poorly understood, and the possibility exists that CSD/PID events might contribute to deterioration.
As of 2003, CSD or PID had been reported in only ten human subjects in two papers (Mayevsky et al., 1996; Strong et al., 2002). Strong et al. reported that transient ECoG suppressions suggestive of depolarisations are common - but by no means universal - after brain injury in humans. Sub-dural ECoG electrode strips were placed in 14 patients who had undergone craniotomy for trauma or intracranial hemorrhage; monitoring was for up to 60 h following the injury. Five of these patients (36%) showed patterns of ECoG depression consistent with PID/CSD in brain regions adjacent to the primary injury.
As of 2008, a number of recent COSBID studies have established that there is a substantial incidence of spontaneous depolarisation events also in patients suffering from aneurysmal subarachnoid haemorrhage (aSAH) (Dreier et al., 2006), malignant hemisphere stroke (MHS) (Dohmen et al., 2008), and intracerebral haematoma (ICH) (Fabricius et al., 2008).