PURPOSE: Topiramate is a novel antiepileptic drug, and is known to act as a glutamate receptor antagonist. Excitotoxicity by glutamate is also advocated as an arm of brain injury in bacterial meningitis. We sought to delineate whether topiramate could attenuate brain energy depletion during bacterial meningitis by near infrared spectroscopy monitoring. METHODS: Meningitis was induced by intracisternal injection of 108 colony forming units of Escherichia coli. Topiramate at a dose of 50 or 100 mg/kg was given to the piglets 30 minutes before the induction of meningitis. The piglets in the meningitis control group were not given topiramate. Cerebral blood volume, cerebral blood flow, and brain cell energy state were monitored for 6 hours by near infrared spectroscopy. RESULTS: 100 mg/kg of topiramate significantly attenuated the increase in intracranial pressure and leukocyte count in the cerebrospinal fluid during study period. Although statistically insignificant, there was a trend of decrease in cerebral blood volume as indicated by total hemoglobin and cerebral blood flow as indicated by oxidized hemoglobin. Deduced hemoglobin in the meningitis was attenuated by topiramate. Topiramate did not significantly affect the brain energy state as indicated by cytochrome aa3 during the 6 hours after the induction of meningitis. CONCLUSION: 100 mg/kg of topiramate significantly attenuated the inflammatory response in experimentally induced bacterial meningitis. However, there was no significant effect of topiramate on the brain cell energy metabolism during the early phase of experimental bacterial meningitis.
Arm ; Blood Volume ; Brain Injuries ; Brain* ; Cerebrospinal Fluid ; Electron Transport Complex IV ; Energy Metabolism* ; Escherichia coli* ; Escherichia* ; Glutamic Acid ; Intracranial Pressure ; Leukocyte Count ; Meningitis ; Meningitis, Bacterial ; Meningitis, Escherichia coli* ; Receptors, Glutamate ; Spectrum Analysis ; Stem Cells

Humans ; Interferon-gamma ; metabolism ; Interleukin-12 Subunit p40 ; metabolism ; Meningitis, Bacterial ; blood ; cerebrospinal fluid ; Multiple Sclerosis, Relapsing-Remitting ; blood ; cerebrospinal fluid ; Staphylococcal Infections ; blood ; cerebrospinal fluid

Adolescent ; C-Reactive Protein ; metabolism ; Cell Aggregation ; Child ; Child, Preschool ; Cytodiagnosis ; methods ; Female ; Humans ; Infant ; Leukocytes ; cytology ; Male ; Meningitis, Bacterial ; blood ; cerebrospinal fluid ; diagnosis ; Meningitis, Viral ; blood ; cerebrospinal fluid ; diagnosis ; Sensitivity and Specificity

In this study, we tested the hypothesis that decreased cerebral perfusion pressure (CPP) induces cerebral ischemia and worsen brain damage in neonatal bacterial meningitis. Meningitis was induced by intracisternal injection of 10(9) colony forming units of Escherichia coli in 21 newborn piglets. Although CPP decreased significantly at 8 hr after bacterial inoculation, deduced hemoglobin (HbD), measured as an index of changes in cerebral blood flow by near infrared spectroscopy, did not decrease significantly. In correlation analyses, CPP showed significant positive correlation with brain ATP and inverse correlation with brain lactate levels. CPP also correlated positively with HbD and oxidized cytochrome aa3 (Cyt aa3) by near infrared spectroscopy. However, CPP did not show significant correlation with cerebral cortical cell membrane Na+,K+-ATPase activity, nor with levels of lipid peroxidation products. In summary, decreased CPP observed in this study failed to induce cerebral ischemia and further brain injury, indicating that cerebrovascular autoregulation is intact during the early phase of experimental neonatal bacterial meningitis.
Animal ; Animals, Newborn ; Blood Glucose/metabolism ; Cell Membrane/microbiology ; Cell Membrane/enzymology ; Cerebral Cortex/metabolism ; Cerebral Cortex/chemistry ; Cerebral Cortex/blood supply ; Cerebrovascular Circulation/physiology* ; Energy Metabolism/physiology* ; Escherichia coli Infections/physiopathology* ; Escherichia coli Infections/metabolism* ; Glucose/cerebrospinal fluid ; Glucose/analysis ; Intracranial Pressure ; Lactic Acid/cerebrospinal fluid ; Lactic Acid/blood ; Lactic Acid/analysis ; Lipid Peroxidation/physiology ; Meningitis, Bacterial/physiopathology* ; Meningitis, Bacterial/metabolism* ; Na(+)-K(+)-Exchanging ATPase/metabolism ; Spectroscopy, Near-Infrared ; Swine

OBJECTIVESNeonates are vulnerable to various infections because of their immature immune responses. Toll-like receptors could induce immune responses, both the innate and the acquired immune responses. The aim of the present study was to investigate the changes of TLR2 and TLR4 in neonatal infections, and to determine their roles in anti-infection immune reaction.

METHODSA total of 200 infants were divided into six groups: sepsis group (n = 21), bacterial pneumonia group (n = 70), bacterial meningitis group (n = 17), urinary tract infection group (n = 38), congenital syphilis group (n = 11) and non-infection group (n = 48). The TLR mRNA was determined by RT-PCR. The protein expression of TLR and the percentage of TLR positive cells were evaluated through flow cytometric analysis.

RESULTS1. The TLR2 mRNA expression increased significantly in the sepsis group (6.14 +/- 0.80), most significantly in the Gram positive sepsis group (6.43 +/- 0.74). TLR2 mRNA expression was also significantly higher in the bacterial pneumonia group (5.49 +/- 0.62), the bacterial meningitis group (5.61 +/- 0.60) and the congenital syphilis group (5.89 +/- 0.38). TLR2 protein expression was the highest in the sepsis group and significantly increased in the bacterial pneumonia group, bacterial meningitis group and the congenital syphilis groups as well, all were higher than the TLR2 protein expression of the non-infectious group (1.27 +/- 0.75). The TLR2 protein expression in the Gram positive bacterial sepsis group was 2.54 +/- 0.68, that of Gram negative bacterial sepsis group was 1.25 +/- 0.51 (P < 0.05). The percentage of TLR2 positive cells in the neonatal infection group was (70.95 +/- 20.15)%, which did not differ significantly from that of non-infection group. 2. The mRNA expression of TLR4 was the highest in the sepsis group (6.20 +/- 1.59), while that in the Gram negative bacterial sepsis group was 6.78 +/- 1.79, higher than that of the Gram positive bacterial sepsis group, 5.39 +/- 0.78, (t = 2.29, P = 0.037). TLR4 mRNA expression increased significantly in the bacterial pneumonia group (5.33 +/- 1.07), the bacterial meningitis group (5.87 +/- 0.70) and the urinary tract infection group (5.38 +/- 0.91). There were no significant differences in TLR4 protein expression among these groups. The percentage of TLR4 positive cells in the neonatal infection groups was (0.71 +/- 0.31)%, higher than that of non- infection group (0.29 +/- 0.36)%. 3. In the Gram positive bacterial sepsis group, the mRNA expression of TLR2 (6.43 +/- 0.74) was higher than the mRNA expression of TLR4 (5.39 +/- 0.78), (t = 1.56, P = 0.024). In the Gram negative bacterial sepsis group, the mRNA expression of TLR4 (6.78 +/- 0.79) was significantly higher than the mRNA expression of TLR2 (5.64 +/- 0.68) (t = 2.63, P = 0.011). In the sepsis group, the TLR2 protein expression was significantly higher than the expression of TLR4 (t = 1.06, P = 0.044). The percentage of TLR4 positive cells was lower than the percentage of TLR2 positive cells among all these groups, P < 0.01. 4. Correlation analysis on gestational age and the mRNA expression, the protein expression and the percentage of TLR2 and TLR4 positive cells among all these groups did not show any statistical significance.

CONCLUSIONSThe mRNA and the protein expression of TLR2 and the mRNA expression of TLR2 increased significantly in the studied neonatal infection groups, especially in the severe sepsis groups. The mRNA expression of TLR2 increased mainly in the Gram positive bacterial infection groups, and the mRNA expression of TLR4 increased in the Gram negative bacterial infection groups, suggesting that both the TLR2 and TLR4 signal pathway took part in the immune mechanism of neonatal infection, providing new idea and experimental basis for further understanding of immune mechanism of neonatal infection.

Gram-Negative Bacterial Infections ; immunology ; Gram-Positive Bacterial Infections ; immunology ; Humans ; Infant, Newborn ; Meningitis, Bacterial ; immunology ; Pneumonia, Bacterial ; immunology ; Sepsis ; immunology ; microbiology ; Syphilis, Congenital ; immunology ; Toll-Like Receptor 2 ; immunology ; metabolism ; Toll-Like Receptor 4 ; immunology ; metabolism ; Urinary Tract Infections ; immunology ; microbiology

OBJECTIVETo explore the neuro-protective effect and mechanism of qingkailing injection (QKL) against cerebral injury caused by E. coli-meningitis (CM).

METHODSThe CM model rabbits were treated by ampicillin with QKL as adjuvant. The leukocyte count and protein content in cerebral spinal fluid (CSF), the contents of water, sodium, potassium and calcium in cerebral tissues were measured before, 16 h and 26 h after Bacillus coli injection respectively. The expression of matrix metalloproteinase-9 (MMP-9) was determined at the same time.

RESULTSAdjunctive treatment with QKL can not only inhibit the increase of leukocyte cells, protein content in CSF, and water, sodium, calcium content in cerebral tissues, but also the decrease of potassium content revealed during simple antibiotic treatment. It also can decrease the expression of MMP-9 in cerebral tissues of rabbits with CM.

CONCLUSIONAs an adjunctive treatment, QKL can prevent transient inflammatory reaction and aggravation of brain injury in CM induced by simple antibiotic treatment, its mechanisms might relate with calcium antagonism and attenuation of MMP-9 expression in brain tissues.

Ampicillin ; therapeutic use ; Animals ; Anti-Bacterial Agents ; therapeutic use ; Brain ; metabolism ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Injections ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; Meningitis, Escherichia coli ; drug therapy ; Neuroprotective Agents ; therapeutic use ; Phytotherapy ; Rabbits

No abstract available.
Aged ; Aneurysm/surgery ; Anti-Bacterial Agents/pharmacology ; Brain Diseases/surgery ; Craniotomy/adverse effects ; DNA, Bacterial/chemistry/genetics/metabolism ; Female ; Flavobacteriaceae Infections/etiology/microbiology ; Flavobacterium/classification/drug effects/*isolation & purification ; Humans ; Meningitis/*diagnosis/microbiology ; Microbial Sensitivity Tests ; Phylogeny ; Postoperative Complications ; Sequence Analysis, DNA