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Evaluation of energetic metabolism in the rat brain after meningitis induction by Klebsiella pneumoniae

  • Tatiana Barichello (a1), Lutiana Roque Simões (a1), Jaqueline S. Generoso (a1), Mirelle M. Carradore (a1), Ana Paula Moreira (a1), Ana Paula Panatto (a1), Caroline S. Costa (a1), Álvaro Steckert Filho (a1), Isabela C. Jeremias (a2), Gisele D. Bez (a2) and Emilio Streck (a2)...



Bacterial meningitis is an infection of the central nervous system characterised by strong inflammatory response. The brain is highly dependent on ATP, and the cell energy is obtained through oxidative phosphorylation, a process which requires the action of various respiratory enzyme complexes and creatine kinase (CK) as an effective buffering system of cellular ATP levels in tissues that consume high energy.


Evaluate the activities of mitochondrial respiratory chain complexes I, II, III, IV and CK activity in hippocampus and cortex of the Wistar rat submitted to meningitis by Klebsiella pneumoniae.


Adult Wistar rats received either 10 µl of sterile saline as a placebo or an equivalent volume of K. pneumoniae suspension. The animals were killed in different times at 6, 12, 24 and 48 h after meningitis induction. Another group was treated with antibiotic, starting at 16 h and continuing daily until their decapitation at 24 and 48 h after induction.


In the hippocampus, the meningitis group without antibiotic treatment, the complex I was increased at 24 and 48 h, complex II was increased at 48 h, complex III was inhibited at 6, 12, 24 and 48 h and in complex IV all groups with or without antibiotic treatment were inhibited after meningitis induction, in the cortex there was no alteration.


Although descriptive, our results show that antibiotic prevented in part the changes of the mitochondrial respiratory chain. The meningitis model could be a good research tool to study the biological mechanisms involved in the pathophysiology of the K. pneumoniae meningitis.


Corresponding author

Professor Tatiana Barichello, PhD, Laboratório de Microbiologia Experimental, PPGCS, UNASAU, Universidade do Extremo Sul Catarinense, 88806–000 Criciúma, SC, Brazil. Tel: +55 48 34312643; Fax: +55 48 3443 4817; E‐mail:


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1Kim, KS. Acute bacterial meningitis in infants and children. Lancet Infect Dis 2010;10:3242.
2Klinger, G, Chin, CN, Beyene, J, Perlman, M. Predicting the outcome of neonatal bacterial meningitis. Pediatrics 2000;106:477482.
3Hussen, AS, Shafran, SD. Acute bacterial meningitis in adults. A 12‐year review. Medicine (Baltimore) 2000;79:360368.
4Ko, WC, Paterson, DL, Sagnimeni, AJ et al. Community‐acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis 2002;8:160166.
5Lu, CH, Chang, WN, Chang, HW. Klebsiella meningitis in adults: clinical features, prognostic factors and therapeutic outcomes. J Clin Neurosci 2002;9:533588.
6Barichello, T, Savi, GD, Simões, LR et al. Evaluation of mitochondrial respiratory chain in the brain of rats after pneumococcal meningitis. Brain Res Bull 2010;82:302307.
7Sahly, H, Podschun, R. Clinical, bacteriological, and serological aspects of Klebsiella infections and their spondylarthropathic sequelae. Clin Diagn Lab Immunol 1997;4:393399.
8Liu, YC, Cheng, DL, Lin, CL. Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med 1986;146:19131916.
9Su, CM, Chang, WN, Tsai, NW, Huang, CR, Wang, HC, Lu, CH. Clinical features and outcome of community‐acquired bacterial meningitis in adult patients with liver cirrhosis. Am J Med Sci 2010;340:452456.
10Tsai, MH, Lu, CH, Huang, CR et al. Bacterial meningitis in young adults in Southern Taiwan: clinical characteristics and therapeutic outcomes. Infection 2006;34:28.
11Tang, LM, Chen, ST, Hsu, WC, Chen, CM. Klebsiella meningitis in Taiwan: an overview. Epidemiol Infect 1997;119:135142.
12Hirst, RA, Kadioglu, A, O'Callaghan, C, Andrew, PW. The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin Exp Immunol 2004;138:195201.
13Leib, SL, Tauber, MG. Pathogenisis of bacterial meningitis. Infect Dis Clin North Am 1999;13:527548.
14Grandgirard, D, Leib, SL. Meningitis en Neonatos: bench to bedside. Clin Perinatol 2010;37:655676.
15Klein, M, Koedel, U, Pfister, HW. Oxidative stress in pneumococcal meningitis: a future target for adjunctive therapy? Prog Neurobiol 2006;80:269280.
16Sellner, J, Täuber, MG, Leib, SL. Pathogenesis and pathophysiology of bacterial CNS infections. Handb Clin Neurol 2010;96:116.
17Tauber, MG, Moser, B. Cytokines and chemokines in meningeal inflammation: biology and clinical implications. Clin Infect Dis 1999;28:112.
18Bessman, SP, Carpenter, CL. The creatine‐creatine phosphate energy shuttle. Annu Rev Biochem 1985;54:831865.
19Schnyder, T, Winkler, H, Gross, H, Eppenberger, HM, Wallimann, T. Crystallization of mitochondrial creatine kinase. Growing of large protein crystals and electron microscopic investigation of microcrystals consisting of octamers. J Biol Chem 1991;266:53185322.
20Wallimann, T, Wyss, M, Brdiczka, D, Nicolay, K, Eppenberger, HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 1992;281:2140.
21Brand, MD, Nicholls, DG. Assessing mitochondrial dysfunction in cells. Biochem J 2011;435:297312.
22Barichello, T, Savi, GD, Silva, GZ et al. Antibiotic therapy prevents, in part, the oxidative stress in the rat brain after meningitis induced by Streptococcus pneumoniae. Neurosci Lett 2010;478:9396.
23Irazuzta, JE, Pretzlaff, RK, Zingarelli, B, Xue, V, Zemlan, F. Modulation of nuclear factor‐kB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 2002;30:25532559.
24Grandgirard, D, Schürch, C, Cottagnoud, P, Leib, SL. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother 2007;51:21732178.
25Hoogman, M, van de Beek, M, Weisfelt, M, de Gans, J, Schmand, B. Cognitive outcome in adults after bacterial meningitis. J Neurol Neurosurg Psychiatry 2007;78:10921096.
26Barichello, T, Silva, GZ, Savi, GD et al. Brain creatine kinase activity after meningitis induced by Streptococcus pneumoniae. Brain Res Bull 2009;80:8588.
27Lowry, OH, Rosebough, NG, Farr, AL, Randall, RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265275.
28Cassina, A, Radi, R. Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996;328:309316.
29Fischer, C, Ruitenbeek, W, Berden, JA. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 1985;153:2336.
30Rustin, P, Chretien, D, Bourgeron, T et al. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:3551.
31Hughes, BP. A method for estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathologic sera. Clin Chim Acta 1962;7:597604.
32Chang, WN, Lu, CH, Huang, CR et al. Clinical characteristics of post‐neurosurgical Klebsiella pneumoniae meningitis in adults and a clinical comparison to the spontaneous form in a Taiwanese population. J Clin Neurosci 2010;17:334338.
33Lu, CH, Chang, WN, Lin, YC et al. Bacterial brain abscess: microbiological features, epidemiological trends and therapeutic outcomes. Q J Med 2002;95:501509.
34Coimbra, RS, Voisin, V, Saizieu Ab, DE et al. Gene expression in cortex and hippocampus during acute pneumococcal meningitis. BMC Biol 2006;4:15.
35Wen, LL, Chiu, CT, Huang, YN, Chang, CF, Wang, JY. Rapid glia expression and release of proinflammatory cytokines in experimental Klebsiella pneumoniae meningoencephalitis. Exp Neurol 2007;205:270278.
36Mitchell, L, Smith, SH, Braun, JS, Herzog, KH, Weber, JR, Tuomanen, EI. Dual phases of apoptosis in pneumococcal meningitis. J Infect Dis 2004;190:20392046.
37Grimwood, K, Anderson, P, Anderson, V, Tan, L, Nolan, T. Twelve year outcomes following bacterial meningitis: further evidence for persisting effects. Arch Dis Child 2000;83:111116.
38Andres, RH, Ducray, AD, Schlattner, U, Wallimann, T, Widmer, HR. Functions and effects of creatine in the central nervous system. Brain Res Bull 2008;76:329343.
39Bénit, P, Lebon, S, Rustin, P. Respiratory‐chain diseases related to complex III deficiency. Biochim Biophys Acta 2009;1793:181185.
40Keightley, JA, Anitori, R, Burton, MD, Quan, F, Buist, NR, Kennaway, NG. Mitochondrial encephalomyopathy and complex III deficiency associated with a stop‐codon mutation in the cytochrome b gene. Am J Hum Genet 2000;67:14001410.
41Mourmans, J, Wendel, U, Bentlage, HA et al. Clinical heterogeneity in respiratory chain complex III deficiency in childhood. J Neurol Sci 1997;49:111117.
42Nau, R, Soto, A, Bruck, W. Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol 1999;58:265274.
43Leib, SL, Heimgartner, C, Bifrare, YD, Loeffler, JM, Täauber, MG. Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res 2003;4:4.
44Wu, UI, Mai, FD, Sheu, JN et al. Melatonin inhibits microglial activation, reduces pro‐inflammatory cytokine levels, and rescues hippocampal neurons of adult rats with acute Klebsiella pneumoniae meningitis. J Pineal Res 2011;50:5970.
45Barichello, T, Silva, GZ, Batista, AL et al. Early antibiotic administration prevents cognitive impairment induced by meningitis in rats. Neurosci Lett 2009;465:7173.



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