Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

BMC Infectious Diseases

Christian Østergaard⁴  Ian J Rowland²  Stephen L Leib³  Christian T Brandt¹  Jon G Holler⁵ 

[1] Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital Hillerød, Dyrehavevej 29, Hillerød, Copenhagen 3400, Denmark;Department of Entomology, University of Wisconsin, Madison, USA;Biology Division, Spiez Laboratory, Federal Office for Civil Protection, Austrasse, Spiez CH-3700, Switzerland;Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, Hvidovre, Copenhagen 2650, Denmark;Department of Infectious Diseases, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, Hvidovre, Copenhagen 2650, Denmark

关键词: Hippocampus;    Apoptosis;    Meningitis;    Oedema;    Volume;    ADC;    Magnetic resonance imaging;   

Others  :  1133952
DOI  :  10.1186/1471-2334-14-240

 received in 2014-01-03, accepted in 2014-04-25,  发布年份 2014

【 摘 要 】

Background

The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus.

Methods

Experimental meningitis in rats was induced by intracisternal injection of live pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti-pneumococcal antibodies (n = 14). T2 and diffusion weighted MR images were used to analyze changes in hippocampus volume and water diffusion (ADC). The results were correlated to ADC of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis.

Results

Both ADC and the volume of hippocampus were significantly increased in meningitis rats compared to uninfected controls (Kruskal-Wallis test, p = 0.0001, Dunns Post Test, p < 0.05), and were significantly increased in meningitis rats with an early onset bacteremia as compared to meningitis rats with attenuated bacteremia (p < 0.05). Hippocampal ADC and the volume and size of brain ventricles were positively correlated (Spearman Rank, p < 0.05), whereas no association was found between ADC or volume and the extent of apoptosis (p > 0.05).

Conclusions

In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly associated with accompanying bacteremia.

【 授权许可】

   
2014 Holler et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Østergaard C, Konradsen HB, Samuelsson S: Clinical presentation and prognostic factors of streptococcus pneumoniae meningitis according the focus of infection. BMC Infect Dis 2005, 5:1-11. BioMed Central Full Text
• [2]Østergaard C, O’Reilly T, Brandt C, Frimodt-Møller N, Lundgren JD: The influence of the blood bacterial load on the meningeal inflammatory response in streptococcus pneumoniae meningitis. BMC Infect Dis 2006, 6:1-7. BioMed Central Full Text
• [3]Pedersen M, Brandt CT, Knudsen GM, Østergaard C, Skinhoj P, Skovsted IC, Frimodt-Moller N, Moller K: The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats. J Cereb Blood Flow Metab 2008, 28:126-134.
• [4]Brandt CT, Frimodt-Møller N, Lundgren JD, Pedersen M, Skovsted IC, Rowland IJ, Østergaard C: Evaluation of anti-pneumococcal capsular antibodies as adjunctive therapy in experimental pneumococcal meningitis. J Antimicrob Chemother 2006, 58:1291-1294.
• [5]Østergaard C, Leib SL, Rowland I, Brandt CT: Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis. BMC Infect Dis 2010, 10:1. BioMed Central Full Text
• [6]Brandt CT, Holm D, Liptrot M, Østergaard C, Lundgren JD, Frimodt-Moller N, Skovsted IC, Rowland IJ: Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis. J Infect Dis 2008, 197:235-244.
• [7]Hughes DC, Raghavan A, Mordekar SR, Griffiths PD, Connolly DJ: Role of imaging in the diagnosis of acute bacterial meningitis and its complications. Postgrad Med J 2010, 86:478-485.
• [8]Nau R, Soto A, Bruck W: Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol 1999, 58:265-274.
• [9]Leib SL, Clements JM, Lindberg RL, Heimgartner C, Loeffler JM, Pfister LA, Tauber MG, Leppert D: Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis. Brain 2001, 124:1734-1742.
• [10]Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Tauber MG: Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res 2003, 54:353-357.
• [11]Brandt CT, Simonsen H, Liptrot M, Sogaard LV, Lundgren JD, Østergaard C, Frimodt-Moller N, Rowland IJ: In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging. BMC Med Imaging 2008, 8:1. BioMed Central Full Text
• [12]Free SL, Li LM, Fish DR, Shorvon SD, Stevens JM: Bilateral hippocampal volume loss in patients with a history of encephalitis or meningitis. Epilepsia 1996, 37:400-405.
• [13]Marks DA, Kim J, Spencer DD, Spencer SS: Characteristics of intractable seizures following meningitis and encephalitis. Neurology 1992, 42:1513-1518.
• [14]de Jonge RC, Swart JF, Koomen I, Rombouts SA, Gemke RJ, Barkhof F, van Furth AM: No structural cerebral differences between children with a history of bacterial meningitis and healthy siblings. Acta Paediatr 2008, 97:1390-1396.
• [15]Bifrare YD, Kummer J, Joss P, Tauber MG, Leib SL: Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis. J Infect Dis 2005, 191:40-45.
• [16]Fishman RA: Brain edema. N Engl J Med 1975, 293:706-711.
• [17]Blankenberg FG: In vivo imaging of apoptosis. Cancer Biol Ther 2008, 7:1525-1532.
• [18]Leib SL, Kim YSM, Ferriero DM, Tauber MG: Neuroprotective effect of excitatory amino acid antagonist kynurenic acid in experimental bacterial meningitis. J Infect Dis 1996, 173:166-171.
• [19]Sotak CH: Nuclear magnetic resonance (NMR) measurement of the apparent diffusion coefficient (ADC) of tissue water and its relationship to cell volume changes in pathological states. Neurochem Int 2004, 45:569-582.