Abstract
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.
Highlights
Increasing evidence suggests that perinatal infection is a risk factor for brain injury in newborns, and certain neurological disorders developed later in life [1,2]
IL-1 receptor antagonist (IL-1ra) Attenuated Neurobehavioral Deficits Induced by Lipopolysaccharide (LPS) Exposure
First we tested whether IL-1ra could ameliorate LPS-induced neurobehavioral deficits in rats
Summary
Increasing evidence suggests that perinatal infection is a risk factor for brain injury in newborns, and certain neurological disorders developed later in life [1,2]. The underlying mechanisms by which a single neonatal LPS exposure results in long-lasting adverse neurological effects are not clear; it appears that such exposure can trigger a chronic neuroinflammatory response, indicated by a persistent microglial activation and elevated interleukin-1β (IL-1β) expression in the substantia nigra (SN) of adult rats (P70) [15]. Based on these findings, we hypothesized that interleukin-1β (IL-1β) may play a central role in mediating a sustained neuroinflammation in our animal model. The aim of the current study is to determine whether IL-1ra provides long-lasting neuroprotection against neonatal LPS-induced chronic inflammation as well as dopaminergic neuronal injury in adult rats
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