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Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus.
J Mol Neurosci. 2015 Jun; 56(2):245-54.JM

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Castro-Torres RD
Laboratorio de Neurobiología Celular y Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Guadalajara, Jalisco, 44421, Mexico.
Chaparro-Huerta V
No affiliation info available
Flores-Soto ME
No affiliation info available
Jave-Suárez L
No affiliation info available
Camins A
No affiliation info available
Armendáriz-Borunda J
No affiliation info available
Beas-Zárate C
No affiliation info available
Mena-Munguía S
No affiliation info available

MeSH

AnimalsHippocampusKainic AcidMaleMicrogliaNeuroprotective AgentsNitric Oxide Synthase Type IIPyridonesRNA, MessengerRatsRats, Wistar

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25854776

Citation

Castro-Torres, Rubén Darío, et al. "Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus." Journal of Molecular Neuroscience : MN, vol. 56, no. 2, 2015, pp. 245-54.
Castro-Torres RD, Chaparro-Huerta V, Flores-Soto ME, et al. Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus. J Mol Neurosci. 2015;56(2):245-54.
Castro-Torres, R. D., Chaparro-Huerta, V., Flores-Soto, M. E., Jave-Suárez, L., Camins, A., Armendáriz-Borunda, J., Beas-Zárate, C., & Mena-Munguía, S. (2015). Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus. Journal of Molecular Neuroscience : MN, 56(2), 245-54. https://doi.org/10.1007/s12031-015-0509-6
Castro-Torres RD, et al. Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus. J Mol Neurosci. 2015;56(2):245-54. PubMed PMID: 25854776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent Rat Hippocampus. AU - Castro-Torres,Rubén Darío, AU - Chaparro-Huerta,Verónica, AU - Flores-Soto,Mario Eduardo, AU - Jave-Suárez,Luis, AU - Camins,Antoni, AU - Armendáriz-Borunda,Juan, AU - Beas-Zárate,Carlos, AU - Mena-Munguía,Salvador, Y1 - 2015/02/18/ PY - 2014/10/27/received PY - 2015/02/01/accepted PY - 2015/4/10/entrez PY - 2015/4/10/pubmed PY - 2016/3/15/medline SP - 245 EP - 54 JF - Journal of molecular neuroscience : MN JO - J Mol Neurosci VL - 56 IS - 2 N2 - 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. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/25854776/Pirfenidone_Attenuates_Microglial_Reactivity_and_Reduces_Inducible_Nitric_Oxide_Synthase_mRNA_Expression_After_Kainic_Acid_Mediated_Excitotoxicity_in_Pubescent_Rat_Hippocampus_ DB - PRIME DP - Unbound Medicine ER -