Bicuculline-Induced Seizures: A Challenge for Optical and Biochemical Modeling of the Cytochrome Oxidase CuA Nirs Signal

The effect of seizures on brain blood flow and metabolism has been extensively studied. However, few studies have focused on mitochondria. We used near infrared spectroscopy (NIRS) to study hemoglobin and cytochrome oxidase changes during seizures, induced by the GABA antagonist bicuculline, in the adult rat. A broadband spectroscopy system was used with the optodes placed across the rat head. We focused on the initial seizures post-bicuculline addition during which oxyhemoglobin (HbO2) increased, deoxyhemoglobin (HHb) decreased and total hemoglobin (Hbtot) increased. The NIRS signal associated with the oxidised CuA centre of mitochondrial cytochrome c oxidase (oxCCO) decreased. At the highest bicuculline doses (0.25 mg/animal) the maximum values recorded were: ΔHbO2 = +19 ± 7 μM; ΔHHb = -12 ± 4 μM; ΔHbtot = +7 ± 4 μM, ΔoxCCO = - 1.7 ± 0.3 μM. These results are broadly in line with other NIRS studies. However, previous measurements of NADH fluorescence indicate oxidation of the mitochondrial redox chain under these conditions. The changes induced by bicuculline provide an interesting challenge to the physics and biochemistry of using NIRS to study mitochondrial redox states in vivo and we explore the possible spectroscopic and/or biochemical meaning of these apparent anomalies. © Springer Science+Business Media, LLC 2009.