Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice

Abstract

Toxoplasma gondii (T. gondii) is a protozoan parasite with the potential of causing severe encephalitis among immunocompromised humans and animals. Our previous study showed that T. gondii induces high nitric oxide (NO) production, high glial activation (GFAP) and neurofilament expressions, leading to severe neurodegeneration in toxoplasma encephalitis (TE) in the central nervous system (CNS). The aim of this experimental study was to investigate ADAMTS-13 expression and apoptosis in CNS and to identify whether they have any correlation with toxoplasmosis neuropathology and neurodegeneration. Mice were infected with ME49 strain T. gondii and the levels of ADAMTS-13, caspase 3, caspase 8, caspase 9, TNFR1 and Bcl-xL expressions were examined in brain tissues by immunohistochemistry, during the development and establishment of chronic infections at 10, 30 and 60 days post-infection. Results of the study revealed that the levels of ADAMTS-13 (P < 0.005), caspase 3 (P < 0.05), caspase 8 (P < 0.05), caspase 9 (P < 0.005) and TNFR1 (P < 0.05) expressions in the brain markedly increased while Bcl-xL expression decreased (P < 0.005). The most prominent finding from our study was that 10, 30 and 60 days post-infection ADAMTS-13 increased significantly and this may play an important role in the regulation and protection of the blood-brain barrier integrity and CNS microenvironment in TE. These results also suggest that T. gondii-mediated apoptosis might play a pivotal role and a different type of role in the mechanism of neurodegeneration and neuropathology in the process of TE. Furthermore, expression of ADAMTS-13 might give an idea of the progress and is critical for diagnosis of this disease. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of T. gondii-infected mice.

Encephalitis is mediated by ROP18 of Toxoplasma gondii , a severe pathogen in AIDS patients

“…Uncontrolled tachyzoite replication may cause severe and potentially life-threatening encephalitis. It is well known that encephalitis caused by T. gondii can be lethal, due to tissue inflammation, apoptosis, and/or necrosis, as well as other complex pathological processes (2,8,10,11,21). However, the mechanism of TE is still unclear despite a variety of hypotheses that have been proposed.…”

“…Increasing evidence indicates that intracellular pathogens and viruses alike often disturb ER homeostasis and lead to the ER stress response during infection (6,7). As an obligate intracellular protozoan, T. gondii has been shown previously to cause ER stress and induce apoptotic cell death (2,(8)(9)(10)(11).…”

Immunological interaction between Giardia cyst extract and experimental toxoplasmosis

“…NO has a neuroprotective effect while above this physiological level, it has a neurotoxic effect, leading to neuronal degeneration or necrosis . Dincel and Kul stated that T. gondii induced severe iNOS expression resulting in severe neurodegeneration and cerebral pathology.…”

“…Neuropathologies detected in Toxoplasma infection are caused not only by the presence of the parasite itself but also by the highly expressed pro‐inflammatory cytokines and NO. Toxoplasma gondii induces apoptosis due to severe NO production …”

Role of nitric oxide and oxidative stress in pathophysiology of liver injury in streptozotocin-induced type 1 diabetic rats

“…NOmediated cytotoxicity was first shown on macrophages and subsequently the synthesis of high level of NO from L-arginine was shown to induce apoptotic cell death (3,4,11,13,34). Liver degenerations in sepsis, hepatitis and ischemia/reperfusion show frequently co-association with NO production at pathological levels (6,22).…”