A restored humoral environment ameliorates acute brain injury after Angiostrongylus cantonensis infection.

Circulating factors in the circulatory system support important functions of living tissues and the body. Parabiosis is a condition in which two living animals are connected using surgical methods and share a single circulatory system. Angiostrongylus cantonensis is the major cause of infectious eosinophilic meningitis, which causes severe damage to the central nervous system (CNS) and immune system. However, the mechanism of immunopathology remains largely unknown. We hypothesize that a restored humoral environment can help relieve damage to the CNS and immune system. In the present study, we found that administration of normal serum significantly reduced mortality, alleviated thymic atrophy and reduced inflammation in the brains of mice infected with A. cantonensis. We further generated parabiotic pairs between two healthy mice, one of which was then orally infected with A. cantonensis. The results showed that compared with singleton mice, mice connected with a healthy parabiotic partner were protected against CNS and immune system damage, as revealed by significantly reduced inflammation in the brain, alleviated thymic atrophy, and decreased expression of proinflammatory cytokines. These findings revealed that a healthy systemic environment can relieve damage to the CNS and immune system in infected mice, suggesting novel therapeutic approaches for diseases involving severe brain and immune system damage.

Acanthocytosis and brain damage in area postrema and choroid plexus: Description of novel signs of Loxosceles apachea envenomation in rats.

Loxocelism is a neglected medical problem that depends on its severity, can cause a cutaneous or viscero-cutaneous syndrome. This syndrome is characterized by hemostatic effects and necrosis, and the severity of the loxoscelism depends on the amount of venom injected, the zone of inoculation, and the species. In the Chihuahuan desert, the most abundant species is L. apachea. Its venom and biological effects are understudied, including neurological effects. Thus, our aim is to explore the effect of this regional species of medical interest in the United States-Mexico border community, using rat blood and central nervous system (CNS), particularly, two brain structures involved in brain homeostasis, Area postrema (AP) and Choroid plexus (PC). L. apachea specimens were collected and venom was obtained. Different venom concentrations (0, 0.178 and 0.87 µg/g) were inoculated into Sprague-Dawley rats (intraperitoneal injection). Subsequently, blood was extracted and stained with Wright staining; coronal sections of AP were obtained and stained with Hematoxylin-Eosin (HE) staining and laminin γ immunolabelling, the same was done with CP sections. Blood, AP and CP were observed under the microscope and abnormalities in erythrocytes and fluctuation in leukocyte types were described and quantified in blood. Capillaries were also quantified in AP and damage was described in CP. L. apachea venom produced a segmented neutrophil increment (neutrophilia), lymphocyte diminishment (leukopenia) and erythrocytes presented membrane abnormalities (acanthocytosis). Extravasated erythrocytes were observed in HE stained sections from both, AP and CP, which suggest that near to this section a hemorrhage is present; through immunohistofluorescence, a diminishment of laminin γ was observed in AP endothelial cells and in CP ependymal cells when these structures were exposed to L. apachea venom. In conclusion, L. apachea venom produced leukopenia, netrophilia and acanthocytosis in rat peripheral blood, and also generated hemorrhages on AP and CP through degradation of laminin γ.

Changes in purine levels associated with cellular brain injury in gerbils experimentally infected with Neospora caninum.

The present study was carried out in order to assess the possible alterations in purine levels of brain, associated neuronal lesions in gerbils experimentally infected with Neospora caninum. For that, gerbils (Meriones unguiculatus) were inoculated with Nc-1 strain of N. caninum, composing two different experiments: Experiment I (EI) and experiment II (EII), where purine levels were measured along with the histopathologic study, on days 7 (EI), 15 and 30 (EII), post-infection (PI). As a result, it was possible to observe that the purine levels (ATP, ADP, AMP, adenosine, inosine and xanthine) in brain in EI are significantly reduced (p < 0.05), while in EII we faced a different pattern, since in the majority the purine levels were significantly increased (p < 0.05) on days 15 (ATP, AMP, adenosine, hypoxanthine and xanthine) and 30 PI (ATP, ADP, AMP, adenosine, and uric acid). Results of brain histopathology did not show histological lesion in animals of EI; however, in gerbils of EII it was possible to verify that the alterations (lesions) were more pronounced in gerbils evaluated on day 30 PI when compared to day 15 PI. Therefore, it was possible to conclude that the purine levels in brain were altered in both experiments, concomitant with the histopathological injuries observed in EII.

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

[Expression of Toll-like receptor 4 in brain tissue of chronic Toxoplasma gondii infection rats and its effect on brain injury].

OBJECTIVE: To explore the expression of Toll-like receptor 4 (TLR4) in brain tissue of chronic Toxoplasma infection rats and its effect on brain injury. METHODS: Ten male SD rats were randomly divided into 2 groups, namely control and infection groups. Each rat in the infection group was intraperitoneal injected with Toxoplasma gondii tachyzoites 10(7)/ml x 2 ml, and that in the control group was injected with 2 ml sterile normal sodium. After 10 weeks, the expression of TLR4 mRNA in the brain was determined by RT-PCR, and the levels of IL-1beta and IL-4 in peripheral blood sera were detected by ELISA. RESULTS: Compared with the control group, the expression of TLR4 gene and the peripheral blood serum level of IL-1beta of rats in the Toxoplasma gondii infection group were both significantly increased, with all P values were less than 0.05, and the level of IL-4 was also increased, but the difference had no statistically significance (P > 0.05). CONCLUSION: TLR4 might be involved in inflammatory reactions of brain injury for chronic Toxoplasma gondii infection rats.