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Published on: February 28, 2021
Myeloperoxidase Nuclear Imaging for Epileptogenesis
Yinian Zhang1, Daniel P Seeburg1, Benjamin Pulli1
1From the Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China (Y.Z., Y.P.); Center for Systems Biology and Department of Radiology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114 (Y.Z., D.P.S., B.P., G.R.W., L.B., W.A., S.S., Y.I., M.A., E.R., A.M., E.J.K., C.W., F.K.S., J.W.C.); and Department of Neurosurgery, Massachusetts General Hospital, Boston, Mass (W.Z.).
Myeloperoxidase (MPO) plays a key role in epilepsy development. Inhibiting MPO can delay seizures and reduce their severity, suggesting MPO is a potential therapeutic target and imaging biomarker for epilepsy.
Area of Science:
- Neuroscience
- Immunology
- Medical Imaging
Background:
- Epileptogenesis, the process by which epilepsy develops, involves complex biological mechanisms.
- Inflammation is increasingly recognized as a contributing factor in the progression of epilepsy.
- Myeloperoxidase (MPO) is an enzyme associated with inflammatory processes.
Purpose of the Study:
- To investigate the role of myeloperoxidase (MPO) in the development of epilepsy (epileptogenesis).
- To evaluate the potential of molecular nuclear imaging for noninvasively mapping brain inflammation in epilepsy.
Main Methods:
- Studies were conducted on pilocarpine-induced epileptic mice treated with an MPO inhibitor or saline.
- In vivo imaging of brain MPO activity was performed using single photon emission computed tomography/computed tomography (SPECT/CT) with Indium-111-labeled tracer.
- Assessment of MPO's role in spontaneous recurrent seizures included clinical, biochemical, and histopathological analyses.
- Human epilepsy and non-epilepsy brain tissue samples were stained for MPO expression.
Main Results:
- MPO and leukocyte levels were elevated in the brains of epileptic mice.
- Inhibition of MPO significantly delayed the onset and reduced the severity of spontaneous recurrent seizures.
- MPO inhibition also decreased mossy fiber sprouting and matrix metalloproteinase activity, indicating MPO acts upstream of these factors.
- In vivo imaging successfully mapped MPO activity in the hippocampus during epileptogenesis.
- Human epilepsy tissue showed positive MPO immunostaining, unlike control tissue.
Conclusions:
- Myeloperoxidase (MPO) is critically involved in epileptogenesis.
- MPO represents a promising therapeutic target for epilepsy treatment.
- MPO can serve as a valuable imaging biomarker for epilepsy, with potential for clinical translation.
