title: Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus.
abstract: Excitotoxicity and neuroinflammation are strongly linked to the progressions of neurodegenerative diseases and acute injuries in the brain. Systematic administration of kainic acid (KA) in rodents causes severe limbic seizures, selective neuronal loss, and neuroinflammation in the hippocampus that are attributed to the excitotoxic process. Our previous report demonstrated the antioxidant and neuroprotective effects of pirfenidone (PFD) after the seizure onset induced by KA intraperitoneal injection. However, the aim of the present study is to analyze whether PFD has anti-inflammatory properties. Thus, pubescent male Wistar rats (30 days old) were exposed to 12 mg/Kg of KA, and the experimental group received KA and a single dose of 325 mg/Kg PFD in an orogastric tube at 90 min after KA exposure. The PFD treatment dramatically reduces the microglial activation observed by isolectin B4 staining and major histocompatibility complex II immunohistochemistry. We also determined that the messenger RNA of inducible nitric oxide synthase was downregulated by PFD treatment as measured 6 h after the KA injection. Our results indicate that the mechanism of neuroprotection after PFD treatment may include a decreased expression of the inducible nitric oxide synthase and reduced microglial activation. These findings suggest that PFD is a potentially useful strategy of the treatment for acute or chronic neurodegenerative diseases.
authors: Laboratorio de Neurobiología Celular y Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Guadalajara, Jalisco, 44421, Mexico.
authors: Rubén Darío
authors: RD
authors: Castro-Torres
authors: Verónica
authors: V
authors: Chaparro-Huerta
authors: Mario Eduardo
authors: ME
authors: Flores-Soto
authors: Luis
authors: L
authors: Jave-Suárez
authors: Antoni
authors: A
authors: Camins
authors: Juan
authors: J
authors: Armendáriz-Borunda
authors: Carlos
authors: C
authors: Beas-Zárate
authors: Salvador
authors: S
authors: Mena-Munguía
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D011728:Pyridones; D012333:RNA, Messenger; C093844:pirfenidone; D052247:Nitric Oxide Synthase Type II; D007608:Kainic Acid