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Peroxisome-proliferator activator receptor γ (PPARγ) has an anti-inflammatory role that inhibits the nuclear factor-κB (NF-κB) pathway and regulates the expressions of pro-inflammatory proteins, whereas its role in parasitic meningoencephalitis remains unknown. In this study we investigated the role of PPARγ and related mechanisms in eosinophilic meningoencephalitis caused by the rat lungworm Angiostrongylus cantonensis. We observed increased protein NF-κB expression in mouse brain tissue using GW9662, which is the specific antagonist of PPARγ, in a mouse model of angiostrongyliasis. Then we investigated NF-κB-related downstream proteins, such as COX-2, NOSs, and IL-1β, with Western blot or enzyme-linked immunosorbent assay and found that the protein expression was upregulated. The results of gelatin zymography also showed that the MMP-9 activities were upregulated. Treatment with GW9662 increased the permeability of the blood-brain barrier and the number of eosinophils in cerebrospinal fluid. These results suggested that in angiostrongyliasis, PPARγ may play an anti-inflammation role in many inflammatory mediators, including NOS-related oxidative stress, cytokines, and matrix metalloproteinase cascade by decreasing the NF-κB action.

Peroxisome proliferator-activated receptor gamma (PPARγ) regulates neuroinflammation, and its agonists act as neuroprotective agents. This study aims to investigate the correlation between PPARγ and proinflammatory enzyme expression in astroglia infected with Toxoplasma gondii tachyzoite in vitro. Our results showed that matrix metalloprotease (MMP)-2, MMP-9, cyclooxygenase-2 (COX-2), prostaglandin (PGE)-2, inducible nitric-oxide synthase (iNOS), and nitric oxide (NO) were significantly increased in T. gondii-infected astroglia. Furthermore, the expression levels of MMP-2, MMP-9, COX-2, PGE-2, iNOS, and NO were significantly decreased by rosiglitazone-a PPARγ agonist. By contrast, the treatment with GW9662, a PPARγ antagonist, efficiently increased the expression levels of MMP-2, MMP-9, COX-2, PGE-2, iNOS, and NO. These results suggested that the treatment with rosiglitazone offers a potential strategy for controlling the inflammatory factors in T. gondii infection.

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection.

Proteasome primarily degrades the unneeded or damaged proteins by proteolysis. Disruption of the brain barrier and its resulting meningoencephalitis caused by Angiostrongylus cantonensis are important pathological events in non-permissive hosts. In this study, the results showed upregulated proteasome during A. cantonensis infection. Occludin degradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. Moreover, confocal immunoflourescence microscopy showed that occludin was co-localized with MMP-9. The infected-mice were treated with proteasomal activity inhibitor MG132 by 1.5 and 3.0 mg/kg/day, which resulted in significantly reduced protein levels of phosphorylated IκBα (P

We identified the relationship between plasma level changes of cathepsin B and cystatin C before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP).We collected blood specimens from 61 adult patients with CAP before and after antibiotic treatment and from 60 healthy controls and measured the plasma concentrations of cathepsin B and cystatin C expression using the enzyme-linked immunosorbent assay (ELISA). The APACHE II, CURB-65, and Pneumonia Severity Index (PSI) scores were determined to assess CAP severity in patients upon initial hospitalization.The results showed a decline in the number of WBCs and neutrophils, with decreases in the concentrations of CRP, cathepsin B, cystatin C, and the cathepsin B/cystatin C ratio being observed after antibiotic treatment. The plasma concentration of cathepsin B correlated with severity of CAP with the PSI score (r=0.290, p=0.025) and the CURB-65 score (r=0.258, p=0.047), respectively. The plasma concentration of cystatin C correlated with the APACHE II score (r=0.523, p0.001), severity of CAP in the PSI score (r=0.721, p0.001) and the CURB-65 score (r=0.609, p0.001), respectively.Cathepsin B and cystatin C may play a role in the diagnosis and clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies.

Angiostrongylus cantonensis has become a global source of infection in recent years, and the differential diagnosis and timely follow-up are crucial in the management of the infection. Magnetic resonance imaging (MRI) has been suggested as a non-invasive technique in characterizing and localizing lesions during the parasitic infections in the brain. Non-invasive diffusion tensor imaging (DTI) can be used to distinguish microscopic cerebral structures but cannot resolve the more complicated neural structure. Several methods have been proposed to overcome this limitation. One such method, generalized q-sampling imaging (GQI), can be applied to a variety of datasets, including the single shell, multi-shell or grid sampling schemes, which are believed to resolve complicated crossing fibers. This study aimed to characterize angiostrongyliasis in the rabbit brain over a 6-week period using anatomical and diffusion MRI, including DTI and GQI. Our anatomical T2WI and R2 mapping results showed that the ventricle size of the rabbit brain increased after A. cantonensis larvae infection, and the DTI and GQI indices both showed pathological changes in the corpus callosum, hippocampus and cortex over a 6-week infection period. These results were consistent with our histopathological findings. Our results demonstrated that the diagnosis of larvae infection using anatomical and diffusion MRI is possible and that follow-up characterization is informative in revealing the effects of angiostrongyliasis in various brain areas. These support the use of anatomical and diffusion MRI was helpful for diagnosis of eosinophilic meningitis caused by A. cantonensis infection. This non-invasive MRI platform could be used to improve the management of eosinophilic meningitis or eosinophilic meningoencephalitis in humans.

Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole kills the nematode larvae staying in the brain. However, the dead larvae are capable of evoking a severe inflammatory response resulting in the brain damage. Matrix metalloproteinase 9 (MMP-9) is associated with the development of meningitis and with the immune inflammatory reaction. Presently, we studied the combination effects of albendazole and GM6001 (a MMP-9 inhibitor) against angiostrongyliasis in BALB/c mice. Co-administration of drugs produced marked effects; to kill the infecting larvae and to block MMP-9 activity. The combination treatment reduced MMP-9 activity by 89.2% in cerebrospinal fluid. The numbers of inflammatory cells increased significantly upon establishment of infection, but subsided upon co-treatment. Significantly fewer larvae were recovered from treated mice than from untreated, infected mice. The present results strongly suggest that co-therapy with albendazole and GM6001 may be an useful approach for the treatment of human angiostrongyliasis.

A 22-kDa protein was increased quantitatively, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis techniques, in lung microsomes prepared from Angiostrongylus cantonensis-infected rats. However, it was almost absent in normal rats. The protein was purified by sequential chromatography on Superdex 200 columns and identified chemically and immunologically as ferritin. Using isoelectric focusing and anion exchange chromatography, it was identified as L ferritin. Distribution of this 22-kDa protein in the lung tissue of A. cantonensis-infected rate was studied by immunocytochemistry. Positively stained cells were mainly infiltrated macrophages. Our results suggest that L ferritin accumulation in the macrophages may be related to the proliferation of connective tissue elements and the inflammatory response to A. cantonensis dwelling in the pulmonary arteries of the rat.

After bathing at a hot spring resort, a 75-year-old man presented to the emergency department because of seizure-like attack with loss of conscious. This is the first case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in Taiwan. PAM was diagnosed based on detection of actively motile trophozoites in cerebrospinal fluid using a wet-mount smear and the Liu's stain. The amoebae were further confirmed by PCR and gene sequencing. In spite of administering amphotericin B treatment, the patient died 25 days later.

Acute bacterial meningitis (ABM) is a serious disease with severe neurological sequelae. The intense calcium-mediated microglial activation and subsequently pro-inflammatory cytokine release plays an important role in eliciting ABM-related oxidative damage. Considering resveratrol possesses significant anti-inflammatory and anti-oxidative properties, the present study aims to determine whether resveratrol would exert beneficial effects on hippocampal neurons following ABM. ABM was induced by inoculating Klebsiella pneumoniae into adult rats intraventricularly. The time-of-flight secondary ion mass spectrometry (TOF-SIMS), Griffonia simplicifolia isolectin-B4 (GSA-IB4) and ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry, enzyme-linked immunosorbent assay as well as malondialdehyde (MDA) measurement were used to examine the calcium expression, microglial activation, pro-inflammatory cytokine level, and extent of oxidative stress, respectively. In ABM rats, strong calcium signaling associated with enhanced microglial activation was observed in hippocampus. Increased microglial expression was coincided with intense production of pro-inflammatory cytokines and oxidative damage. However, in rats receiving resveratrol after ABM, the calcium intensity, microglial activation, pro-inflammatory cytokine and MDA levels were all significantly decreased. Quantitative data showed that much more hippocampal neurons were survived in resveratrol-treated rats following ABM. As resveratrol successfully rescues hippocampal neurons from ABM by suppressing the calcium-mediated microglial activation, therapeutic use of resveratrol may act as a promising strategy to counteract the ABM-induced neurological damage.

Background The purpose here was to detect the association among plasma matrix metalloproteinase-9 (MMP-9) concentration, single nucleotide polymorphisms (SNPs) of MMP-9 gene and community-acquired pneumonia (CAP). Methods The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively used to measure the plasma MMP-9 level and its gene polymorphisms. Results The level of plasma of MMP-9 was elevated in patients with CAP as compared to that of normal controls and decreased significantly after treatment. Plasma MMP-9 concentration was significantly correlated with white blood cell (WBC) and neutrophil counts in patients with CAP. No significant difference was found in the genotypes distribution of MMP-9 SNPs, rs3918242, rs17576 or rs2274756, between patients with CAP and normal controls. Plasma MMP-9 concentration was not associated with MMP-9 polymorphism. When the cut-off level of the plasma MMP-9 concentration was set to be 105.02 ng/mL, the odds ratio of plasma MMP-9 for CAP risk was 9.86 (95% confident interval: 4.27-22.75). Plasma MMP-9 level may act as a prediction marker for CAP. Conclusions Elevated plasma MMP-9 could be a biological marker for the diagnosis and be a new strategy for target therapy of community-acquired pneumonia.

Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we showed that A. cantonensis-caused eosinoplia and inflammation might lead to the induction of NF-kappaB and protooncogene expression via activation of the tyrosine phosphorylation signal pathway. After mice were infected daily with 30 third-stage larvae of A. cantonensis by oral adminstration for 6 weeks, no significant differences PKC-alpha, MEK-1, ERK-2, JNK, and p38 protein expression were found between the control and infected mice. However, the protein tyrosine phosphorylation levels, NF-kappaB, and iNOS protein products were significantly increased by 3.5-, 3.3-, and 6.3-fold, respectively, after 3 weeks of A. cantonensis infection. The same pattern was found for c-Myc, c-Jun, and c-Fos proteins, which were elevated by 3.2-, 2.3-, and 3.4-fold, respectively, compared to control animals after 3 weeks. The expression potency of these proteins started increasing in week 1, reaching maximal induction in week 3, and then declining in week 5 after A. cantonensis infection. Another consistent result was noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in brain tissues of infected mice. These data suggest that the development of brain injury by eosinophlia of A. cantonensis infection is associated with NF-kappaB and/or nuclear protooncogenes expression, which is activated by the tyrosine phosphorylation pathway.