Spreading depolarization (SD) is the generic term for all waves of abrupt, near-complete breakdown of the neuronal transmembrane ion gradients that cause cytotoxic edema and propagate at about 3 mm/min in cerebral gray matter. The SD continuum describes the spectrum from short-lasting SDs in metabolically intact tissue to SDs of intermediate duration to terminal SD in severely ischemic tissue. Accordingly, SDs occur in human diseases; from the harmless migraine aura to stroke to circulatory arrest. This means that there are overlaps but also large variations in mechanistic aspects along the continuum. For example, SD induces either transient hyperperfusion variably followed by mild oligemia in normal tissue (normal neurovascular response) or severe hypoperfusion (inverse neurovascular response = spreading ischemia) variably followed by hyperemia in tissue at risk for progressive injury.1Dreier, J. P. (2011). “The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.” Nat. Med 17(4): 439-447.
Spreading depolarization imaged using PeriCam PSI. The absolute perfusion (top row) can be visualized and quantified and using the specially developed difference image mode (bottom row), the change in perfusion caused by the SD wave can be followed in a spectacular way
Dreier, J. P. (2011). “The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.” Nat. Med 17(4): 439-447.
Center for Stroke Research Berlin, Charité University Medicine Berlin
Prof. Dr. med. Jens P. Dreier Charité University Medicine Berlin, Germany Center for Stroke Research Berlin
The inverse neurovascular response to SD is observed as a spreading perfusion deficit causing prolongation of SD (Dreier 2011). Laser Speckle Contrast Analysis (LASCA or LSCI) is an ideal tool to differentiate the normal (fig. 1) from the inverse neurovascular response to SD (fig. 2) because it visualizes the perfusion changes in space and time, and is easily combined with various electrophysiological methods to measure, for example, SD or additional variables such as tissue partial pressure of oxygen.