Spreading depolarizations cycle around and enlarge focal ischaemic brain lesions

Abstract

How does infarction in victims of stroke and other types of acute brain injury expand to its definitive size in subsequent days? Spontaneous depolarizations that repeatedly spread across the cerebral cortex, sometimes at remarkably regular intervals, occur in patients with all types of injury. Here, we show experimentally with in vivo real-time imaging that similar, spontaneous depolarizations cycle repeatedly around ischaemic lesions in the cerebral cortex, and enlarge the lesion in step with each cycle. This behaviour results in regular periodicity of depolarization when monitored at a single point in the lesion periphery. We present evidence from clinical monitoring to suggest that depolarizations may cycle in the ischaemic human brain, perhaps explaining progressive growth of infarction. Despite their apparent detrimental role in infarct growth, we argue that cycling of depolarizations around lesions might also initiate upregulation of the neurobiological responses involved in repair and remodelling.

Rho-Kinase Inhibition Improves Ischemic Perfusion Deficit in Hyperlipidemic Mice

“…We and many other groups have shown that PIDs worsen ischemic tissue perfusion and expand the perfusion defect in a stepwise manner. 12,24 Therefore, fewer PIDs may indeed be an additional mechanism by which ROCK inhibition improves ischemic tissue perfusion. However, decreased PID occurrence may also be a consequence of smaller perfusion defects; this needs further testing.…”

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

“…However, vasoconstriction further from the core (red section of arrow) is less severe or sustained, probably allowing repolarization from this event, but leaving tissue at this location vulnerable to a future depolarization. The net effect is shown in panel 4, with the core now expanded to include the original penumbral point of depolarization (Nakamura et al, 2010). Figure 4 Normal and inverse response to cortical spreading depression (CSD) in patients with aneurysmal subarachnoid hemorrhage (aSAH).…”

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

“…[10][11][12][13] SD is a pathological mechanism for secondary injury that drives expansion of the primary brain lesion into the penumbra. [9][10][11][12][13][14][15] Incidence of SD is significantly correlated with poor patient outcomes, including death, vegetative state, and severe disability. 7-9 SD disrupts the concentration gradients of ions and molecules between intra-and extracellular spaces, and repolarization after SD requires vast amounts of energy.…”

“…7-9 Clusters of SD impose particularly severe energy demands on the injured brain. [15][16][17][18] Clinical microdialysis enables monitoring of the local metabolic status of brain tissue in patients with TBI. [18][19][20][21][22][23][24] Boutelle and coworkers developed a rapid sampling microdialysis (rsMD) system that monitors SD-associated glucose transients with 30-s temporal resolution.…”