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 \r<br />was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects \r<br />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 \r<br />(P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to \r<br />P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, \r<br />loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 \r<br />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.
Pang, Y., Tien, L. T., Zhu, H., Shen, J., Wright, C. F., Jones, T. K., … Fan, L. W. (2015). Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats. International Journal of Molecular Sciences, 16(4), 8635–8654. https://doi.org/10.3390/ijms16048635