Activated M1 microglia secrete proinflammatory cytokines into damaged brain areas. The present study examined activated M1 microglial morphology and expression in the hippocampal Cornu Ammonis (CA) 1 region, which is vulnerable to transient ischemia. Transient cerebral ischemia was performed for 5 min in gerbils, and neuronal death in the CA1 region following transient cerebral ischemia was confirmed using cresyl violet staining, neuronal nuclear antigen immunohistochemistry and Fluoro‑Jade B histofluorescent staining. In addition, CA1 regions were stained for cluster of differentiation (CD) 74, a marker for activated M1 microglia and a ligand for macrophage migration inhibitory factor In sham‑operated animals, no CD74 immunoreactivity was observed in the hippocampal CA1 region. CD74 immunoreactivity was not observed in the hippocampal CA1 region until 3 days post‑ischemic insult; however, elevated CD74 immunoreactivity was detected in the CA1 region from 5 days post‑ischemia. Double immunofluorescence staining for CD74 and ionized calcium‑binding adapter molecule 1, a marker for M1 microglial cells, confirmed the expression of CD74 on this microglial subtype. These results indicated that M1 microglia are activated late in the hippocampal CA1 region following ischemic stroke. Therefore, optimizing the timing of therapeutic intervention may reduce activated M1 microglial-induced neuronal damage.

Dendropanax morbifera Léveille has been employed for the treatment of infectious diseases using folk medicine. In this study, we evaluated the antioxidant effects of a leaf extract of Dendropanax morbifera Léveille in the hippocampus of mercury-exposed rats. Seven-week-old Sprague–Dawley rats received a daily intraperitoneal injection of 5 μg/kg dimethylmercury and/or oral Dendropanax morbifera Léveille leaf extract (100 mg/kg) for 4 weeks. Animals were sacrificed 2 h after the last dimethylmercury and/or leaf extract treatment. Mercury levels were measured in homogenates of hippocampal tissue, a brain region that is vulnerable to mercury toxicity. In addition, we measured reactive oxygen species production, lipid peroxidation levels, and antioxidant levels in these hippocampal homogenates. Treatment with Dendropanax morbifera Léveille leaf extract significantly reduced mercury levels in hippocampal homogenates and attenuated the dimethylmercury-induced increase in the production of reactive oxygen species and formation of malondialdehyde. In addition, this leaf extract treatment significantly reversed the dimethylmercury-induced reduction in the hippocampal activities of Cu, Zn-superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase. These results suggest that a leaf extract of Dendropanax morbifera Léveille had strong antioxidant effects in the hippocampus of mercury-exposed rats.

Dendropanax morbifera Léveille is used in herbal medicine as a cancer treatment. In this study, we investigated the effects of Dendropanax morbifera stem extract (DMS) on cadmium (Cd) excretion from the blood and kidney and brain tissues of rats exposed to cadmium, as well as the effects of DMS on oxidative stress and antioxidant levels in the hippocampus after Cd exposure. Seven-week-old Sprague-Dawley rats were exposed to 2 mg/kg of cadmium by intragastric gavage and were orally administered 100 mg/kg of DMS for 4 weeks. Animals were sacrificed and Cd determination was performed using inductively coupled plasma mass spectrometry. In addition, the effects of Cd and/or DMS on oxidative stress were assayed by measuring reactive oxygen species production, protein carbonyl modification, lipid peroxidation levels, and antioxidant levels in hippocampal homogenates. Exposure to Cd significantly increased Cd content in the blood, kidneys, and hippocampi. DMS treatment significantly reduced Cd content in the blood and kidneys, but not in the hippocampi. Exposure to Cd significantly increased reactive oxygen species production, protein carbonyl modification, lipid peroxidation, total sulfhydryl content, reduced glutathione content, and glutathione reductase activity. In contrast, Cu, Zn-superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activity in the hippocampus were significantly decreased after exposure to Cd, and administration of DMS significantly inhibited these Cd-induced changes. These results indicate that DMS facilitates cadmium excretion from the kidneys, reduces cadmium-induced oxidative stress in the hippocampus, and modulates SOD1, CAT, GPx, and glutathione-S-transferase activities.