Myeloperoxidase Nuclear Imaging for Epileptogenesis

Abstract

q RSNA, 2015 Purpose:To determine if myeloperoxidase (MPO) is involved in epileptogenesis and if molecular nuclear imaging can be used to noninvasively map inflammatory changes in epileptogenesis. Materials and Methods:The animal and human studies were approved by the institutional review boards. Pilocarpine-induced epileptic mice were treated with 4-aminobenzoic acid hydrazide (n = 46), a specific irreversible MPO inhibitor, or saline (n = 42). Indium-111-bis-5-hydroxytryptamide-diethylenetriaminepentaacetate was used to image brain MPO activity (n = 6 in the 4-aminobenzoic acid hydrazide and saline groups; n = 5 in the sham group) by using single photon emission computed tomography/computed tomography. The role of MPO in the development of spontaneous recurrent seizures was assessed by means of clinical symptoms and biochemical and histopathologic data. Human brain specimens from a patient with epilepsy and a patient without epilepsy were stained for MPO. The Student t test, one-way analysis of variance, and Mann-Whitney and Kruskal-Wallis tests were used. Differences were regarded as significant if P was less than .05. Results:MPO and leukocytes increased in the brain during epileptogenesis (P , .05). Blocking MPO delayed spontaneous recurrent seizures (99.6 vs 142 hours, P = .016), ameliorated the severity of spontaneous recurrent seizures (P , .05), and inhibited mossy fiber sprouting (Timm index, 0.31 vs 0.03; P = .003). Matrix metalloproteinase activity was upregulated during epileptogenesis in an MPO-dependent manner (1.44 vs 0.94 U/mg, P = .049), suggesting that MPO acts upstream of matrix metalloproteinases. MPO activity was mapped during epileptogenesis in vivo in the hippocampal regions. Resected temporal lobe tissue from a human patient with refractory epilepsy but not the temporal lobe tissue from a patient without seizures demonstrated positive MPO immunostaining, suggesting high translational potential for this imaging technology. Conclusion:The findings of this study highlight an important role for MPO in epileptogenesis and show MPO to be a potential therapeutic target and imaging biomarker for epilepsy.q RSNA, 2015

Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis

“…We show an increase in MPO activity in positive control animals, as reported previously [56]. However, treatment with zingerone alleviated MPO content, indicating the anti-inflammatory role of zingerone, as reported [57].…”

The many roles of myeloperoxidase: From inflammation and immunity to biomarkers, drug metabolism and drug discovery

“…SPECT/CT imaging confirmed that MPO activity was inhibited. Also, MPO was present in the temporal lobe of an epileptic patient, which was absent in controls [ 149 ]. Studies on the role of MPO in brain injury are essential, but so is the specific type of injury.…”

Activation of the phagocyte NADPH oxidase/NOX2 and myeloperoxidase in the mouse brain during pilocarpine-induced temporal lobe epilepsy and inhibition by ketamine

“…Superoxide generates hydrogen peroxide (H 2 O 2 ), a substrate of myeloperoxidase (MPO), an enzyme found in phagocytes and mainly in neutrophils (Hernandes and Britto 2012). NOX2derived reactive oxygen species (ROS) and MPO are suggested to be involved in a variety of processes of epileptogenesis and constitute an extremely deleterious event considered to be a cause and consequence of prolonged seizures (Zhang et al 2016).…”