Catastrophic consequences: can the feline parasite Toxoplasma gondii prompt the purrfect neuroinflammatory storm following traumatic brain injury?

Abstract

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide; however, treatment development is hindered by the heterogenous nature of TBI presentation and pathophysiology. In particular, the degree of neuroinflammation after TBI varies between individuals and may be modified by other factors such as infection. Toxoplasma gondii, a parasite that infects approximately one-third of the world's population, has a tropism for brain tissue and can persist as a lifelong infection. Importantly, there is notable overlap in the pathophysiology between TBI and T. gondii infection, including neuroinflammation. This paper will review current understandings of the clinical problems, pathophysiological mechanisms, and functional outcomes of TBI and T. gondii, before considering the potential synergy between the two conditions. In particular, the discussion will focus on neuroinflammatory processes such as microglial activation, inflammatory cytokines, and peripheral immune cell recruitment that occur during T. gondii infection and after TBI. We will present the notion that these overlapping pathologies in TBI individuals with a chronic T. gondii infection have the strong potential to exacerbate neuroinflammation and related brain damage, leading to amplified functional deficits. The impact of chronic T. gondii infection on TBI should therefore be investigated in both preclinical and clinical studies as the possible interplay could influence treatment strategies.

Serum Biomarker Concentrations upon Admission in Acute Traumatic Brain Injury: Associations with TBI Severity, Toxoplasma gondii Infection, and Outcome in a Referral Hospital Setting in Cameroon

“…Toxoplasma gondii positivity was observed in 33% of cases, with a median age of 30 (23,39) years, similar to reports in the literature where one third of the world population is said to be infected with T. gondii [40][41][42]. S100B levels were higher in T. gondii-positive patients.…”

“…However, the potential elevation of serum levels of S100B in neuro-inflammation after TBI should not be overlooked, but instead, further studies with larger sample sizes and more accurate laboratory methods may help to clarify the possible effects of T. gondii on S100B serum or plasma concentrations. Furthermore, experimental studies have shown that T. gondii infection reduces cerebral microvascular perfusion and induces neuro-inflammation through activation of the cerebral endothelial cells [40,41]. These results support the concept that latent neuro-parasitic disease, like T. gondii infection, might aggravate the disease process in acute neurological disorders, which could be reflected in biomarker concentrations.…”

“…We hypothesized that a latent T. gondii infection might influence the neuropathology in traumatic brain injury. Recent literature attests that latent infections with T. gondii may cause neuro-inflammation, which could worsen the neuro-inflammatory component of TBI [40]. However, it has not yet been experimentally established how T. gondii affects the brain in TBI.…”

Two Billion Infected: An Inexpensive Method to Measure Latent Toxoplasmosis and its Economic Consequences*

“…The method we propose, however, can also be seen as a diagnostic tool for latent Toxoplasmosis infections. While less clinically relevant than the acute condition, latent infections are still of primary importance as they are characterized by low-grade persistent neuroinflammation and cardiovascular injury (Egorov et al, 2021), can act as a reservoir for acute-stage reactivation causing disease in immunocompromised patients and might exacerbate the extent of brain damage after traumatic brain injury (Robert-Gangneux and Dardé, 2012;Baker et al, 2024). Crucially, about three-quarters of new infections in healthy individuals are asymptomatic (Weiss and Dubey, 2009).…”