Circulating concentrations, cerebral output of the CINC-1 and blood­brain barrier disruption in Wistar rats after pneumococcal meningitis induction.

Pneumococcal meningitis is a severe infectious illness of the central nervous system (CNS), with high rates of lethality and morbidity, being that the microorganism and the host's inflammatory response are responsible for cerebral complications. Moreover, the blood­brain barrier (BBB) itself secretes cytokines and, because of the bipolar nature of the BBB, these substances can be secreted into either the CNS compartment or in the blood, so patients with acute bacterial meningitis frequently develop sepsis. Therefore, the aim of this study was to evaluate the cytokine/chemokine levels in different vessels and the BBB integrity after pneumococcal meningitis induction. Wistar rats were infected with Streptococcus pneumoniae, and the BBB integrity was investigated using Evan's blue dye. Also, blood from the carotid artery and jugular vein was collected in order to perform tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-60 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) analyses by enzyme-linked immunosorbent assay (ELISA). CINC-1 levels were increased at 6 h in the arterial plasma and at 3 and 6 h in the jugular plasma. We observed BBB breakdown between 12 and 24 h in the hippocampus and at 12 and 18 h in the cortex after pneumococcal meningitis induction. The increase of CINC-1 occurred prior to the BBB breakdown. CINC-1 is a neutrophil chemoattractant and it may be related to early events in the pneumococcal meningitis pathophysiology.

Increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 10(6) parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.

Increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria.

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 106 parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.

Differential vulnerability of the rat retina, suprachiasmatic nucleus and intergeniculate leaflet to malnutrition induced during brain development.

We investigated in young rats the effects of malnutrition on the main structures of the circadian timing system: retina, hypothalamic suprachiasmatic nuclei (SCN), thalamic intergeniculate leaflet, retinohypothalamic- and geniculohypothalamic tracts. Control rats were born from mothers fed a commercial diet since gestation, and malnourished rats from mothers fed a multideficient diet since gestation (GLA group) or lactation (LA group). After weaning, pups received the same diet as their mothers, and were analysed at postnatal days 27, 30-33 and 60-63. Brain sections were processed to visualise in the SCN neuropeptide Y immunoreactivity and terminal labeling after intraocular tracer injections. Nissl staining was used to assess cytoarchitectonic boundaries of the SCN and cell features in retinal whole mounts. Cell counts, morphometric and densitometric analysis were performed. Compared with controls, the total retinal surface was reduced and the topographical distribution of retinal ganglion cells was altered in malnourished rats, with changes in their density. Alterations were also detected in the SCN dimensions in the GLA and LA groups at one and two postnatal months, as well as in the SCN portion occupied by the retinal input in the GLA group at days 30-33, but not in the NPY-containing geniculohypothalamic tract. The present data point to subtle changes, with a low and differential vulnerability to early malnutrition, of structures involved in circadian timing regulation. Furthermore, the present findings suggest that the altered circadian rhythmicity previously documented in malnourished rats cannot be ascribed to impaired development of the retino- and geniculohypothalamic projections to the SCN.