Dynamic Changes of Hepatocyte Growth Factor in Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

Hepatocyte growth factor (HGF) is a member of the angiogenic growth factor family, which exerts a variety of effects on epithelial, endothelial, and neuronal cells by binding to the c-MET receptor tyrosine kinase. It was reported that HGF attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier (BBB) and decreases in expression of tight junction proteins in cerebral vessels of rats. Studies on the localization of the c-Met/HGF recep- tor in the rat brain and the interaction with HGF after brain injuries show that HGF plays an important role as a neu- rotrophic factor in the brain. To assess the role of HGF in patients with eosinophilic meningitis, a retrospective, cohort study was conducted to measure the dynamic changes of HGF in the cerebrospinal fluid (CSF) and blood of nine patients with eosinophilic meningitis. The mean HGF CSF at presentation, 1 week, 2 weeks, and 3 weeks after admission was 539 pg/ mL, 540 pg/mL, 376 pg/mL, and 279 pg/mL, respectively. The mean level of HGF CSF at presentation (539 ± 242 pg/mL) and 1 week after admission (540 ± 213 pg/mL) was significantly higher than in controls (162 ± 207 pg/mL)( P = 0.02 and P = 0.01, respectively). The CSF/blood ratio of HGF at presentation (0.61) was higher when compared with physiologic situations in uninfected individuals (0.51). The levels of HGF in CSF were not correlated with the amount of CSF cells or proteins. All patients recovered without neurologic sequelae. These results indicate that high concentrations of HGF in the CSF occur in eosinophilic meningitis, and may have a role in protecting against endothelial injury and reducing BBB dysfunction. Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis in the Pacific Islands and Southeast Asia. Human infection occurs after ingestion of the worms in raw snails or fish that serve as intermediate hosts. Rats serve as the definitive host of the nematode. If an infection occurs in non-permissive hosts, including humans and mice, the develop- ment of the parasites will terminate at the young-adult worm stage in the brain and cause eosinophilic meningitis or menin- goencephalitis. 1-6 Lee and others 7 showed that dysfunction of the blood-brain barrier (BBB) occurred in mice infected with A. cantonensis , evident by the high concentrations of protein and albumin, high leukocyte counts in the cerebrospinal fluid (CSF), a high ratio of CSF/serum protein and albumin, and high permeability of the BBB. Infection in the CSF causes a severe inflammatory reaction, mediated by pathogen products and host cytokines. This inflammatory reaction compromises the function of BBB, resulting in the exudation of plasma pro- teins and development of vasogenic brain edema, which con- tributes to cerebral dysfunction and brain damage. 8,9