Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

Abstract

Abstract-To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFN␥). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFN␥ brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia.

Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

“…For example, it inhibits the development of arthritis in mice deficient in the interleukin receptor antagonist (IL1RN) [106]. T. gondii infection is also able to reduce infarct size in focal cerebral ischaemia in mice, an effect attributed to the ability of infection to increase the expression of nerve growth factor, as well as that of anti-inflammatory cytokines and of glutathione and oxidative stress protective genes, while reducing the expression of proinflammatory cytokines [107]. …”

Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic ParasiteToxoplasma gondiias a Novel Tool

“…Toxoplasma is an intracellular parasite that naturally, persistently, and asymptomatically infects the CNS of both humans and rodents. Three studies have shown that mice chronically infected with one particular strain of Toxoplasma are protected against a second CNS insult ( Arsenijevic et al., 2007 ; Jung et al., 2012 ; Möhle et al., 2016 ). Two of these studies found a > 60% reduction in Aβ deposition in infected mice compared with uninfected AD mice ( Jung et al., 2012 ; Möhle et al., 2016 ).…”

Suppression of inflammation in ischemic and hemorrhagic stroke: therapeutic options

“…This response is analogous to (and overlaps with) ischemic or hyperthermic preconditioning, in which sublethal prestroke stimuli up-regulate a coordinated network of protective genes [31]. Chronic prestroke inflammation can also be protective: chronic preischemic stroke infection of mice with Toxoplasma gondii reduced the subsequent proinflammatory cytokine response, improving outcome and lessening infarct size [32]. Similar results were also shown more recently following induced periodontitis in rats [33].…”