Effects of agmatine on hypoxic microglia and activity of nitric oxide synthase

Microglia are the resident macrophages of CNS and play a crucial role in maintaining homeostasis against various neuronal injuries. However, excessive activation of microglia may destroy healthy neurons as well as damaged neurons. We investigated neuroprotective effects of amgatine on hypoxic microglia using in vitro and in vivo models for transient hypoxia. For in vitro study, BV2 immortalized murine microglia were incubated with or without 100 mu M of agmatine in a closed anaerobic chamber for 2 h. After recovery in normoxic condition for 20 h, cell viability and the amount of nitrite generation were determined. For in vivo study, 100 mg/kg of agmatine or equivalent volume of saline was intraperitoneally administered, and the left middle cerebral artery of adult male Sprague-Dawley rats was occluded for 90 mm. After 24 h from occlusion, the cortex and striatum of the forebrains was evaluated to check the immunoreactivity with a microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), and inducible nitric oxide synthase (iNOS). Results showed that agmatine attenuated hypoxia-induced cytotoxicity and nitrite production by BV2 microglia. Agmatine also decreased the activities of microglia and NOS induced by transient middle cerebral artery occlusion. Finally, our findings reveal that agmatine may reduce microglial damages caused by transient hypoxia and suggest that agmatine may lead to a novel therapeutic strategy for hypoxic neuronal injuries. (c) 2010 Elsevier B.V. All rights reserved.