Research article

Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice

Chien-Wei Liao^1,2* , Chia-Kwung Fan^2,3* , Ting-Chang Kao^2,3 , Dar-Der Ji⁴ , Kua-Eyre Su⁵ , Yun-Ho Lin⁶ and Wen-Long Cho^1*

¹  Institute of Tropical Medicine, National Yang-Ming University School of Medicine, 155 Li-Nong St., Sec. 2, Taipei 112, Taiwan

²  Department of Parasitology, Taipei Medical University College of Medicine, 250 Wu-Hsing St., Taipei 110, Taiwan

³  Graduate Institute of Medical Sciences, Taipei Medical University College of Medicine, 250 Wu-Hsing St., Taipei 110, Taiwan

⁴  Laboratory of Parasitic Diseases, Center for Diseases Control, Department of Health, 161 Kun-Yang St., Taipei 100, Taiwan

⁵  Department of Parasitology, National Taiwan University College of Medicine, 1 Jen-Ai Rd., Sec. 1, Taipei 100, Taiwan

⁶  Department of Pathology, Taipei Medical University College of Medicine, 250 Wu-Hsing St., Taipei 110, Taiwan

author email corresponding author email* Contributed equally

BMC Infectious Diseases 2008, 8:84doi:10.1186/1471-2334-8-84

Published:	24 June 2008

Abstract

Background

Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor β1 (TGF-β1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), β-amyloid precursor proteins (AβPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT.

Methods

BIAB expressions and UPS function in the brains of mice inoculated with a single dose of 250 T. canis embryonated eggs was investigated from 3 days (dpi) to 8 weeks post-infection (wpi) by Western blotting and RT-PCR.

Results

Results revealed that at 4 and 8 wpi, T. canis larvae were found to have invaded areas around the choroid plexus but without eliciting leukocyte infiltration in brains of infected mice; nevertheless, astrogliosis, an indicator of BI, with 78.9~142.0-fold increases in GFAP expression was present. Meanwhile, markedly increased levels of other BIAB proteins including TGF-β1, S100B, NF-L, tTG, AβPP, and tau, with increases ranging 2.0~12.0-fold were found, although their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impairment was evidenced by the overexpression of conjugated ubiquitin and ubiquitin in the brain.

Conclusion

Further studies are needed to determine whether there is an increased risk of CT progression into neurodegenerative disease because neurodegeneration-associated AβPP and phosphorylated tau emerged in the brain.