Increased TSPO expression, pyroglutamate-modified amyloid beta (AßN3(pE)) accumulation and transient clustering of microglia in the thalamus of Tg-SwDI mice.

Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aß in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies. In the present study, we documented interesting new features in the thalamus of Tg-SwDI mice: 1) a sharp increase in the expression of ionized calcium-binding adapter molecule 1 (Iba-1) in microglia in 6-month-old animals; 2) microglia clustering at six months that disappeared in old animals; 3) N-truncated/modified AßN3(pE) peptide in 9-month-old female and 12-month-old male mice; 4) an age-dependent increase in translocator protein (TSPO) expression. These findings reinforce the versatility of this model for studying multiple pathological issues involved in AD and CAA.

Sodium thiosulphate attenuates brain inflammation induced by systemic lipopolysaccharide administration in C57BL/6J mice.

It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration. STS reduced brain levels of pro-inflammatory cytokine interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), ionized calcium binding adaptor molecule 1 (Iba-1) and 18 kDa translocator protein (TSPO) in an animal model of systemic LPS-induced neuroinflammation. In addition, we demonstrated for the first time elevated TSPO expression in retinal ganglion cells layer after peripheral LPS challenge and inhibition of ocular TSPO expression after treatment with STS. We think that STS may be used as an adjuvant anti-inflammatory therapy for many pathological conditions associated with inflammation in the brain.

Alpha-mangostin attenuates brain inflammation induced by peripheral lipopolysaccharide administration in C57BL/6J mice.

Neuroinflammation is an important feature in the pathogenesis and progression of neurodegenerative diseases. Molecules with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated that alpha-mangostin (α-MG), a natural xanthone purified from mangosteen pericarp, reduced brain levels of pro-inflammatory cytokine interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and 18 kDa translocator protein (TSPO) in an animal model of peripheral LPS-induced neuroinflammation. We think that evaluation of α-MG as an adjuvant treatment in preclinical models of AD, PD, multiple sclerosis and other diseases with known shared pathology merits further consideration.