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Received Oct 26, 2017; Revised Feb 3, 2018; Accepted Mar 8, 2018
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1. Introduction
Neuroinflammation plays a critical role in Parkinson’s disease and other neurodegenerative diseases [1, 2]. The main hallmark of neuroinflammation in Parkinson’s disease is the presence of activated microglia in the substantia nigra of humans [3] and animal models of that disease [4–6]. Similar to macrophages, activated microglia can phagocytose, present antigens through the major histocompatibility complex (MHC) class II [2, 7], synthesize, and release humoral factors such as cytokines, chemokines, reactive oxygen-nitrogen species, complement cascade proteins, and prostaglandins [8–11]. The tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1, and IL-6 transform astrocytes into proliferative immunological cells, recruited in the inflamed brain area [12–15]. The participation of glial cells in the neuroinflammation of Parkinson’s disease has been characterized to a large extent in animal models generated by neurotoxins such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or rotenone [5, 16–19]. These potent neurotoxins primarily cause the death of dopaminergic neurons, so they have not favored the clarification whether neuroinflammation is the cause or consequence of dopaminergic neurodegeneration. Lipopolysaccharide (LPS) appears to be a neuroinflammatory stimulus more suitable to mimic the acute response of microglia that might also occur in the early stage of Parkinson’s disease [20].
LPS is a major component of the outer membrane of gram-negative bacteria and a potent inducer of inflammation via activation of toll-like receptor 4 (TLR4) [21], not only in peripheral tissues and organs [22, 23] but also in the central nervous system (CNS) [24, 25]. Studies using systemic injection [26] or ventricular infusion of LPS [24] in rodents have shown accumulation of activated microglia in various brain nuclei mainly in the substantia nigra, thus suggesting that LPS can be useful to study neurodegeneration as a model of Parkinson’s disease [24, 25]. LPS injected directly into the substantia nigra can elicit a strong macrophage/microglial local reaction that is followed by the specific death of nigral dopaminergic neurons, thus suggesting that LPS can cause neuronal cell death indirectly through the inflammatory reaction [25, 27]. A recent study has confirmed...