Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have
shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite-
laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a
compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain.
Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the
epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded
Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical
imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the
rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated
Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling
overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes
into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and
380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater
nanoparticle accumulation within the liver and the spleen (p<0.05).
Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used
for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds.
The effect of seizures on monocyte biodistribution should be further explored to better
understand the systemic effects of epilepsy.