Fig. 5: Mechanisms of postlesional slow waves.
From: Sleep-like cortical dynamics during wakefulness and their network effects following brain injury
Many events associated with structural brain damage can converge in engaging cortical bistability during wakefulness. The first class of events involves the enhancement of activity-dependent adaptation mechanisms mediated by Ca++- and Na+-gated K+ currents in cortical neurons (top panel). These include brainstem and midbrain lesions or compressions (left), subcortical nuclei and/or white matter lesions (middle), as well as diffuse axonal injury of traumatic etiology (right). In all these instances, the influence of wake-promoting neuromodulators (e.g., cholinergic and noradrenergic) is strongly decreased, and in some cases, virtually absent. This leads to a predominance of adaptation currents in cortical areas downstream of the structural lesion. The second class of events involves a critical loss of lateral excitatory fibers, which can bring areas that are near or connected to the lesion site into a state of disfacilitation, whereby local inhibition prevails over projected excitatory influences (bottom panel). This occurs in the case of cortico-subcortical structural lesions, which can affect both local (left) and long-range (middle) cortico-cortical connections, as well as in the case of diffuse axonal injury, involving lateral fibers (right). In addition to structural disconnections, other mechanisms, such as acute edema and inflammatory processes (left panel), can lead to the generation of postlesional slow waves, via the local activation of microglia and astrocytes together with the expression of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNFɑ). Finally, metabolic events induced by ischemia, such as the reduction of the ATP/ADP ratio (right panel), strongly activate K-ATP sensitive channels causing membrane hyperpolarization and suppression of activity in local neuronal populations surrounding the lesion. All these events, alone or in combination, may converge in favoring OFF-periods and slow waves during wakefulness in cortical areas topologically related to the site of injury.
