Preictal and Ictal Neurovascular and Metabolic Coupling Surrounding a Seizure Focus

Abstract

Epileptic events initiate a large focal increase in metabolism and cerebral blood flow (CBF) to the ictal focus. In contrast, decreases in CBF have been demonstrated surrounding the focus, the etiology of which is unknown i.e. arising either from active shunting of blood or passive steal. The relationship between these events and neuronal activity and metabolism are also unknown. We investigated neurovascular and neurometabolic coupling in the ictal surround using optical imaging of light scattering and cerebral blood volume, autofluorescence imaging (AFI) of flavoproteins, direct measurements of CMRO2 and two-photon imaging of blood vessel diameter in a rat model of ictal events elicited with focal injection of 4-aminopyridine. We discovered a novel phenomenon, in which ictal events are preceded by pre-ictal vasoconstriction of blood vessels in the surround, occurring 1–5 s before seizure onset, which may serve to actively shunt oxygenated blood to the imminently hypermetabolic focus or may be due to small local decreases in metabolism in the surround. Early ictal hypometabolism, transient decreases in cell swelling and CBV in the surround are consistent with early ictal surround inhibition as a precipitating event in seizure onset as well as shaping the evolving propagating ictal wavefront, although the exact mechanism of these cerebraovascular and metabolic changes is currently unknown. AFI was extremely sensitive to the ictal onset zone and may be a useful mapping technique with clinical applications.

Fluorescence lifetime microscopy of NADH distinguishes alterations in cerebral metabolism in vivo

“…Reports have demonstrated that the localized application of GABA A antagonist BMI yields pronounced disinhibition, yielding increased excitatory signaling with consequent changes in metabolism and blood flow that vary with time and distance from the focal seizure location [54][55][56]. Studies continue to elucidate the specific details and mechanisms of focal seizure-induced neurovascular alterations in the center and surrounding areas [56,57]. Investigators have reported conflicting observations concerning the metabolic response to seizure activity in vivo.…”

Neurovascular Interactions in the Neurologically Compromised Neonatal Brain

“…Although the haemodynamic response is much longer than the electrographic assessment of seizure duration, it is remarkably consistent across seizure events, predominantly consisting of an initial increase, then prolonged decrease of blood volume. The reconstructed DOT images exhibit complex spatial dynamics reminiscent of a number of animal studies, which have shown an 'inhibitory surround' phenomenon associated with epileptic foci [18][19][20].…”

Spatial landscape of oxygen in and around microvasculature during epileptic events

“…In both animal models and patients, the epileptic events can evoke drastic increases in CBF to meet the high metabolic demand caused by this intense neuronal activity. [9][10][11] Measures of oxygen partial pressure (PO 2 ) in tissue during seizures have displayed an initial dip with various methods 12,13 but the spatial landscape of this phenomenon has not been thoroughly documented. Recent data showed that most capillaries released little oxygen at baseline acting as an oxygen reserve that was recruited during increased neuronal activity.…”