Approximately two billion people worldwide are chronically infected with T. gondii and yet with largely unknown consequences. On the other hand, several authors reported an association between
migraine and
patent foramen ovale (PFO), and different types of
headaches, including
migraine, may be precipitated by various diseased states or medications associated with marked immune irregularities, which sometimes cause reactivation of latent
cerebral toxoplasmosis (CT). Recently, in a group of 104 subjects with
migraine, 46 individuals (44.2%) were found to be seropositive for T. gondii. PFO,
atrial septal defects, as well as pulmonary right-to-left shunts are usually associated with a various degree of arterial blood
oxygen desaturation.
Hypoxia is associated with an increase in the generation of several proinflammatory
cytokines and other
inflammation mediators, such as
TNF-alpha, IL-1-beta,
IL-6,
IL-8,
chemokines (
monocyte chemoattractant protein-1,
CC-chemokine receptor 2,
macrophage inflammatory protein-1alpha,
intercellular adhesion molecule-1),
acute-phase protein gene expressions, COX-2 gene transcription, induction of iNOS, and
reactive oxygen species. Moreover,
hypoxia markedly decreased T-lymphocyte
IL-2 mRNA, a key
cytokine responsible for B-cell proliferation and
immunoglobulin secretion, and ischemic tissues demonstrated intravascular neutrophil accumulation, vascular damage, and increased vascular wall permeability. Interestingly, T. gondii activates
hypoxia-inducible factor 1 already at physiologically relevant
oxygen levels and requires HIF1 for growth and survival. These abnormalities may cause imbalance in the host/T. gondii immune system, which finally results in the reactivation of CT. In addition,
hypoxia may participate in paradoxical microembolism because arterial
oxygen desaturation enhances expression of
plasminogen activator inhibitor-1, an important factor which suppresses fibrinolysis, and this effect may be further amplified by a decreased expression of
plasminogen activators, finally causing blood
hypercoagulability and paradoxical microembolism. In summary, further studies are required to verify the above-presented pathomechanisms probably responsible for the association between PFO and the development of
migraine. It is possible that some migraineurs with PFO may benefit from evaluation and treatment of
toxoplasmosis in the future once more information is known.