Neurovascular regulation is critical for metabolic recovery from spreading depression.

Abstract

This scientific commentary refers to ‘Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma’ by Hinzman et al. (doi:10.1093/awu241). Long after Leao’s 1944 description of spreading depression in rabbit neocortex, scepticism remained over whether this phenomenon could be evoked or observed in the human brain (Somjen, 2001). Although many investigations have been carried out into the initiation, occurrence and spread of spreading depression, the mechanisms of ionic current flow underlying depolarization, and treatment paradigms (Pietrobon and Moskowitz, 2014), it is only recently that recording and imaging techniques have been able to confirm the occurrence of spreading depression in damaged human cortex, particularly in conditions involving trauma, subarachnoid haemorrhage, stroke, and possibly migraine headache with aura (Lauritzen et al. , 2011; Eikermann-Haerter et al. , 2012; Woitzik et al. , 2013). The intense depolarization and loss of ionic gradients in large volumes of brain tissue experiencing spreading depression means that significant substrate and metabolic capacity is required to generate energy for cell recovery (Somjen, 2001). If this metabolic need is unmatched by substrate supply (through neurovascular induction of increased blood flow), then propagation of brain damage can occur (Hossmann, 1994). In this issue of Brain , Hinzman and colleagues report a critical deficit in neurovascular coupling when spreading depression occurs near a traumatic brain lesion, in which decreased blood flow occurs in response to spreading depression (i.e. inverse neurovascular coupling) instead of increased blood flow, limiting the brain’s ability to meet the intense metabolic demand (Hinzman et al. , 2014). Although Hinzman and colleagues’ combined blood flow and electrocorticographic (ECoG) recording techniques only effectively worked in 5 of 24 patients, the spectrum of enhanced versus inverted neurovascular coupling in these five patients provides us with excellent examples of how proximity to a developing brain …