Microglia activation: one of the checkpoints in the CNS inflammation caused by Angiostrongylus cantonensis infection in rodent model

Abstract

Angiostrongylus cantonensis (A. cantonensis) is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats; humans are non-permissive hosts like the mice. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningo-encephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of hosts to parasite during A. cantonensis invasion and development. To further understand the reasons why mice and rats attain different outcomes in A. cantonensis infection, we used the HE staining to observe the pathological changes of infected mice and rats. In addition, we measured mRNA levels of some cytokines (IL-5, IL-6, IL-13, Eotaxin, IL-4, IL-10, TGF-β, IFN-γ, IL-17A, TNF-α, IL-1β, and iNOS) in brain tissues of mice and rats by real-time PCR. The result showed that brain inflammation in mice was more serious than in rats. Meanwhile, mRNA expression levels of IL-6, IL-1β, TNF-α, and iNOS increased after mice were infected. In contrast, mRNA levels of these cytokines in rats brain tissues decreased at post- infection 21 days. These cytokines mostly were secreted by activated microglia in central nervous system. Microglia of mice and rats were showed by Iba-1 (microglia marker) staining. In micee brains, microglia got together and had more significant activation than in rats brains. The results demonstrate that mice and rats have different CNS inflammation after infection by A. cantonensis, and it is in line with other researchers' reported findings. In conclusion, it is suggested that microglia activation is probably to be one of the most important factors in angiostrongyliasis from our study.

Nitric oxide and cytokine production by glial cells exposed in vitro to neuropathogenic schistosome Trichobilharzia regenti

“…Interestingly, microglia cultures did not significantly raise production of IL-6 and TNF-α following exposure to HSF, although they are generally considered proinflammatory cells in the CNS. For example, they were suggested to be crucial players in mediating inflammation in murine cerebral angiostrongylosis [48]. However, no IL-6 and TNF-α secretion was detected after murine microglia were grown in the medium containing soluble factors from Mesocestoides corti metacestodes which are used as a murine model for neurocysticercosis [49].…”

Selective Reduction of Brain Docosahexaenoic Acid after Experimental Brain Injury and Mitigation of Neuroinflammatory Outcomes with Dietary DHA

“…106 In rat models of abdominal surgery and of parasite infection, significant changes in IL-1β and microglia activation were detected in the brain 3 weeks after insult, but changes in IL-6 were not detected. 107,108 Although we did not observe an IL-6 response, it is intriguing that IL-1β, 99,109 IL-6, 110,111 TNF-α, 112,113 IL-10, and TGF-β 114 have all been linked to pain mechanisms or headaches via calcitonin gene-related peptide. Post-traumatic headaches can increase the amount of time needed for cognitive recovery from TBI, 115 are often part of PCS, 26 and can be associated with sensory hypersensitivity 24 and inflammatory cytokines.…”

“…Such outcomes would be consistent with both the short-term effects 18,[20][21][22]48,103,118 of DHA and/or omega-3 fatty acids on cognition after TBI as well as when either is available throughout an entire, longer term TBI experiment in rodents. 91,108 It should be noted, again, that rodents convert 18:3n -3 to DHA significantly better than humans do. [60][61][62][63] Another possibility is that lateral FPI, controlled cortical impact, and the impact-acceleration weight-drop models are all known to cause lesions and swelling of the brain parenchyma, which does not typically occur after midline FPI.…”

Hallazgos Histopatológicos en el Sistema Nervioso Central de Rattus norvegicus Infectados con Angiostrongylus cantonensis

“…Wang et al (2008) no observaron cambios evidentes a los 7 dpi, pero encontraron algunas células inflamatorias que se incrementaron en las meninges a los 14 dpi y otras aparecieron en el cerebro después de 21 dpi en ratas infectadas con A. cantonensis. Asimismo, Wei et al (2015) demostraron que los ratones y las ratas infectadas con A. cantonensis exhiben sínto-mas conductuales evidentes del SNC, aunque leves, y desaparecen a las tres semanas de la infección. Es posible que las diferencias con el presente estudio estén relacionadas a una diferente respuesta inmune, pues los cambios de comportamiento fueron observados en los 48, 49, 56 y 60 dpi.…”