Interleukin-1 Receptor Antagonist Reduces Neonatal Lipopolysaccharide-Induced Long-Lasting Neurobehavioral Deficits and Dopaminergic Neuronal Injury in Adult Rats

International Journal of Molecular Sciences

Yi Pang¹  Lu-Tai Tien²  Hobart Zhu¹  Juying Shen¹  Camilla F. Wright¹  Tembra K. Jones¹  Samir A. Mamoon¹  Abhay J. Bhatt¹  Zhengwei Cai¹  Lir-Wan Fan¹ 

[1] Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; E-Mails:;School of Medicine, Fu Jen Catholic University, Xinzhuang Dist, New Taipei City 24205, Taiwan; E-Mail:

关键词: lipopolysaccharide;    interleukin-1 receptor antagonist;    dopaminergic neuronal injury;    substantia nigra;    microglia;   

DOI  :  10.3390/ijms16048635

来源: mdpi

【 摘 要 】

Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.