The
14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious
meningitis and
Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual
isoforms in response to parasitic eosinophilic
meningitis. The purposes of this study were to determine the
14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic
meningitis. Mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and sacrificed every week for 3 consecutive weeks after
infection. The
Evans blue method and BBB junctional
protein expressions were used to measure changes in the BBB.
Hematoxylin and
eosin staining was used to analyze pathological changes in the mice brains following 1-3 weeks of
infection with A. cantonensis. The levels of
14-3-3 protein isoforms in serum/CSF and brain homogenates were analyzed by Western blot, and immunohistochemistry (IHC) was used to explore the different
isoform distributions of
14-3-3 proteins and changes in BBB junctional
proteins in the mice brain meninges.
Dexamethasone was injected intraperitoneally from the seventh day post
infection (dpi) until the end of the study (21 dpi) to study the changes in BBB junctional
proteins. The amounts of
Evans blue, tight junction and
14-3-3 protein isoforms in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. There were significant increases in
14-3-3 protein isoforms β and γ in the CSF in the second and third weeks after
infection compared to the controls and first week of
infection, which were correlated with the severity of BBB damage in brain histology, and
Evans blue extravasation. Using IHC to assess the distribution of
14-3-3 protein isoforms and changes in BBB junctional
proteins in the mice brain meninges, the expressions of
isoforms β, γ, ε, and θ and junctional
proteins occludin and
claudin-5 in the brain meninges increased over a 3-week period after
infection compared to the controls and 1 week after
infection. The administration of
dexamethasone decreased the expressions of BBB junctional
proteins occludin and
claudin-5 in the mice brain meninges. Our findings support that
14-3-3 proteins β and γ can potentially be used as a CSF marker of neuronal damage in parasitic eosinophilic
meningitis caused by A. cantonensis.