A LIGHT MICROSCOPY STUDY OF THE MIGRATION OFNAEGLERIA FOWLERIFROM THE NASAL SUBMUCOSA TO THE CENTRAL NERVOUS SYSTEM DURING THE EARLY STAGE OF PRIMARY AMEBIC MENINGOENCEPHALITIS IN MICE

Abstract

The migratory pathway of Naegleria fowleri from the nasal submucosa to the central nervous system (CNS) during the early stage of primary amebic meningoencephalitis (PAM) was investigated in mice. Twenty-one-day-old CD-1 mice were inoculated by intranasal instillation of 1 x 10(6) amebas. Animals were divided into 3 groups of 5 and, after being anesthetized, were killed at intervals of 24, 32, and 48 hr postinoculation by transcardial perfusion with formaldehyde, acetic acid, and methanol. The heads were decalcified, divided in the midsagittal plane, and the area of the cribriform plate removed and embedded in paraffin. Serial sections were cut at 8 microm and stained with a combination of celestin blue, Harris' hematoxylin, and acid fuchsin for light microscopy. Focal inflammation and amebas were observed in the submucosal nerve plexus, olfactory nerves penetrating the cribriform plate, and the olfactory bulb of the brain as early as 24 hr postinoculation. The time periods selected assured that the disease process would not obliterate soft tissue structures. Earlier studies used moribund mice in which the inflammation and the number of amebas were overwhelming. The present study provides convincing evidence that amebas gain initial access to the CNS through olfactory nerves within the cribriform plate during the early stages of PAM.

Particle-size dependent effects in the Balb/c murine model of inhalational melioidosis

“…Direct infection of the brain via retrograde axonal transport through the olfactory neurone from the nasal cavity has been observed with viruses, bacteria, and protozoans including Japanese encephalitis virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, Influenza virus, Equine herpesvirus-9, Streptococcus pneumoniae , Neisseria meningitidis , Balamuthia mandrillaris and Naegleria fowleri (Danes et al, 1973a,b,c; Martinez, 1977; Jarolim et al, 2000; van Ginkel et al, 2003; Kiderlen and Laube, 2004; Roy et al, 2009; Yamada et al, 2009; El-Habashi et al, 2010; Sjölinder and Jonsson, 2010; Steele and Twenhafel, 2011; Schrauwen et al, 2012). Even prions have been demonstrated to shed into the nasal cavity from the brain using the reverse of this transport process (Corona et al, 2009; Bessen et al, 2010).…”

Particle size and pathogenicity in the respiratory tract

“…In eastern equine encephalitis virus (EEEV) the olfactory neuronal pathway is important for inhalational but not parenteral routes of infection in rodent models 74 , 92 . Utilization of the olfactory neurone to cross the cribriform plate into the central nervous system has also been observed in URT infection models for Nipah virus, Japanese encephalitis virus, Hendra virus, herpes simplex virus, influenza virus (H5N1 subtype), Borna virus, Balamuthia mandrillaris , Naegleria fowleri , B. pseudomallei , Streptococcus pneumoniae , Listeria monocytogenes , and Neisseria meningitidis 77 , 87 , 96 - 105 . Interestingly, recently differential phagocytosis of Escherichia coli and Burkholderia thailandensis was observed in vitro by olfactory sheathing and Schwann cells perhaps representing a mechanism for colonization, infection, or clearance 155 …”

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

“…PAM affects the central nervous system (CNS), progresses rapidly, and is commonly fatal. In experimental animals, the amoebae gain access to the CNS by crossing the olfactory bulbs [97, 98]. Once there, the trophozoites divide rapidly and cause inflammation associated with tissue destruction, leading to death in a few days.…”