1-1-diphenyl-2-picrylhydrazyl and Infarction--Middle-Cerebral-Artery

The preventive effect of Anemarrhena asphodeloides Bunge (Liliaceae), a traditional Chinese medicine, on ischemia-reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. Water extract of Anemarrhena asphodeloides (WEAA) was orally administered promptly prior to and 2 h after reperfusion. Total infarct volume and edema in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with WEAA in a dose-dependent manner (p<0.05). The therapeutic time window of WEAA was 3 h in this ischemia-reperfusion rat model. WEAA also significantly inhibited increased neutrophil infiltration of ischemic brain tissue as estimated by myeloperoxidase (MPO) activity and immunohistochemical analysis. MPO-positive cells were markedly reduced by WEAA administration in striatal and cortical areas. These findings suggest that WEAA plays a crucial protective role in ischemia-induced brain injury, and suggest that WEAA could serve as a lead medicinal herb for the development of neuroprotective agents following transient focal ischemic brain injury.

Topics: Anemarrhena; Animals; Biphenyl Compounds; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Free Radical Scavengers; Hydrazines; Immunohistochemistry; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Male; Neuroprotective Agents; Neutrophil Infiltration; Peroxidase; Picrates; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Rhizome; Saponins; Time Factors; Triterpenes

The neuroprotective effects of minocycline-which is broadly protective in neurologic-disease models featuring cell death and is being evaluated in clinical trials-were investigated both in vitro and in vivo. For the in vivo study, focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice. Minocycline at 90 mg/kg intraperitoneally administered 60 min before or 30 min after (but not 4 h after) the occlusion reduced infarction, brain swelling, and neurologic deficits at 24 h after the occlusion. For the in vitro studies, we used cortical-neuron cultures from rat fetuses in which neurotoxicity was induced by 24-h exposure to 500 microM glutamate. Furthermore, the effects of minocycline on oxidative stress [such as lipid peroxidation in mouse forebrain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. Minocycline significantly inhibited glutamate-induced cell death at 2 microM and lipid peroxidation and free radical scavenging at 0.2 and 2 microM, respectively. These findings indicate that minocycline has neuroprotective effects in vivo against permanent focal cerebral ischemia and in vitro against glutamate-induced cell death and that an inhibition of oxidative stress by minocycline may be partly responsible for these effects.

Topics: Animals; Antioxidants; Benzimidazoles; Benzoxazoles; Biphenyl Compounds; Brain Edema; Brain Infarction; Cell Death; Cell Survival; Cells, Cultured; Cerebral Cortex; Chromans; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Fluorescent Dyes; Glutamic Acid; Hydrazines; Infarction, Middle Cerebral Artery; Inhibitory Concentration 50; Ischemia; Lipid Peroxidation; Male; Mice; Minocycline; Neurons; Neuroprotective Agents; Oxidative Stress; Picrates; Quinolinium Compounds; Saponins; Tetrazolium Salts; Time Factors