Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.pdf
Author preprint (520.13 kB)
This is an electronic version (Author’s preprint) of an article published in Brain Research ;2006 Nov 22;1121(1):35-45.The original published version is available at: http://www.sciencedirect.com/science/journal/00068993
[en] Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Fukui, On; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Kinugasa, Yukiko; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Fukuda, Aya; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Fukuda, Hirotsugu; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Tskitishvili, Ekaterine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement > Osaka University Graduate School of Medicine, Department of Obstetrics and Gynecology
Hayashi, Shusaku; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Song, Mihyon; Kawasaki Medical School > Department of Obstetrics and Gynecology
Kanagawa, Takeshi; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Hosono, Takayoshi; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Shimoya, Koichiro; Kawasaki Medical School > Department of Obstetrics and Gynecology
Murata, Yuji; Osaka University Graduate School of Medicine > Department of Obstetrics and Gynecology
Language :
English
Title :
Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.
Akita K., Ohtsuki T., Nukada Y., Tanimoto T., Namba M., Okura T., Takakura-Yamamoto R., Torigoe K., Gu Y., Su M.S., Fujii M., Satoh-Itoh M., Yamamoto K., Kohno K., Ikeda M., and Kurimoto M. Involvement of caspase-1 and caspase-3 in the production and processing of mature human interleukin 18 in monocytic THP.1 cells. J. Biol. Chem. 272 (1997) 26595-26603
Allan S.M., and Rothwell N.J. Cytokines and acute neurodegeneration. Nat. Rev., Neurosci. 2 (2001) 734-744
Allan S.M., and Rothwell N.J. Inflammation in central nervous system injury. Philos. Trans. R. Soc. London, Ser. B Biol. Sci. 358 (2003) 1669-1677
Barone F.C., and Feuerstein G.Z. Inflammatory mediators and stroke: new opportunities for novel therapeutics. J. Cereb. Blood Flow Metab. 19 (1999) 819-834
Barone F.C., Arvin B., White R.F., Miller A., Webb C.L., Willette R.N., Lysko P.G., and Feuerstein G.Z. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28 (1997) 1233-1244
Bazan J.F., Timans J.C., and Kastelein R.A. A newly defined interleukin-1?. Nature 379 (1996) 591
Bona E., Hagberg H., Loberg E.M., Bagenholm R., and Thoresen M. Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short- and long-term outcome. Pediatr. Res. 43 (1998) 738-745
Bona E., Andersson A.L., Blomgren K., Gilland E., Puka-Sundvall M., Gustafson K., and Hagberg H. Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. Pediatr. Res. 45 (1999) 500-509
Bramlett H.M., Green E.J., Dietrich W.D., Busto R., Globus M.Y., and Ginsberg M.D. Posttraumatic brain hypothermia provides protection from sensorimotor and cognitive behavioral deficits. J. Neurotrauma 12 (1995) 289-298
Busto R., Globus M.Y., Dietrich W.D., Martinez E., Valdes I., and Ginsberg M.D. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 20 (1989) 904-910
Clark R.K., Lee E.V., Fish C.J., White R.F., Price W.J., Jonak Z.L., Feuerstein G.Z., and Barone F.C. Development of tissue damage, inflammation and resolution following stroke: an immunohistochemical and quantitative planimetric study. Brain Res. Bull. 31 (1993) 565-572
Clifton G.L., Jiang J.Y., Lyeth B.G., Jenkins L.W., Hamm R.J., and Hayes R.L. Marked protection by moderate hypothermia after experimental traumatic brain injury. J. Cereb. Blood Flow Metab. 11 (1991) 114-121
Conti B., Park L.C., Calingasan N.Y., Kim Y., Kim H., Bae Y., Gibson G.E., and Joh T.H. Cultures of astrocytes and microglia express interleukin 18. Brain Res. Mol. Brain Res. 67 (1999) 46-52
Cowell R.M., Xu H., Galasso J.M., and Silverstein F.S. Hypoxic-ischemic injury induces macrophage inflammatory protein-1alpha expression in immature rat brain. Stroke 33 (2002) 795-801
Dalmau I., Vela J.M., Gonzalez B., Finsen B., and Castellano B. Dynamics of microglia in the developing rat brain. J. Comp. Neurol. 458 (2003) 144-157
Davis E.J., Foster T.D., and Thomas W.E. Cellular forms and functions of brain microglia. Brain Res. Bull. 34 (1994) 73-78
Deng H., Han H.S., Cheng D., Sun G.H., and Yenari M.A. Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke 34 (2003) 2495-2501
Derugin N., Wendland M., Muramatsu K., Roberts T.P., Gregory G., Ferriero D.M., and Vexler Z.S. Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats. Stroke 31 (2000) 1752-1761
Edwards M.J., Saunders R.D., and Shiota K. Effects of heat on embryos and foetuses. Int. J. Hyperthermia 19 (2003) 295-324
Fantuzzi G., and Dinarello C.A. Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J. Clin. Immunol. 19 (1999) 1-11
Felderhoff-Mueser U., Schmidt O.I., Oberholzer A., Buhrer C., and Stahel P.F. IL-18: a key player in neuroinflammation and neurodegeneration?. Trends Neurosci. 28 (2005) 487-493
Fitzgerald K.A., and O'Neill L.A. The role of the interleukin-1/Toll-like receptor superfamily in inflammation and host defence. Microbes Infect. 2 (2000) 933-943
Fukuda H., Tomimatsu T., Watanabe N., Mu J.W., Kohzuki M., Endo M., Fujii E., Kanzaki T., and Murata Y. Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia-ischemia. Brain Res. 910 (2001) 187-191
Ghayur T., Banerjee S., Hugunin M., Butler D., Herzog L., Carter A., Quintal L., Sekut L., Talanian R., Paskind M., Wong W., Kamen R., Tracey D., and Allen H. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386 (1997) 619-623
Gu Y., Kuida K., Tsutsui H., Ku G., Hsiao K., Fleming M.A., Hayashi N., Higashino K., Okamura H., Nakanishi K., Kurimoto M., Tanimoto T., Flavell R.A., Sato V., Harding M.W., Livingston D.J., and Su M.S. Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science 275 (1997) 206-209
Hagberg H., Gilland E., Bona E., Hanson L.A., Hahin-Zoric M., Blennow M., Holst M., McRae A., and Soder O. Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats. Pediatr. Res. 40 (1996) 603-609
Hedtjarn M., Leverin A.L., Eriksson K., Blomgren K., Mallard C., and Hagberg H. Interleukin-18 involvement in hypoxic-ischemic brain injury. J. Neurosci. 22 (2002) 5910-5919
Hedtjarn M., Mallard C., Eklind S., Gustafson-Brywe K., and Hagberg H. Global gene expression in the immature brain after hypoxia-ischemia. J. Cereb. Blood Flow Metab. 24 (2004) 1317-1332
Hedtjarn M., Mallard C., and Hagberg H. Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia. J. Cereb. Blood Flow Metab. 24 (2004) 1333-1351
Hedtjarn M., Mallard C., Arvidsson P., and Hagberg H. White matter injury in the immature brain: role of interleukin-18. Neurosci. Lett. 373 (2005) 16-20
Hedtjarn M., Mallard C., Iwakura Y., and Hagberg H. Combined deficiency of IL-1beta18, but not IL-1alphabeta, reduces susceptibility to hypoxia-ischemia in the immature brain. Dev. Neurosci. 27 (2005) 143-148
Ivacko J.A., Sun R., and Silverstein F.S. Hypoxic-ischemic brain injury induces an acute microglial reaction in perinatal rats. Pediatr. Res. 39 (1996) 39-47
Jander S., Schroeter M., and Stoll G. Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response. J. Cereb. Blood Flow Metab. 22 (2002) 62-70
Johnston M.V., Trescher W.H., and Taylor G.A. Hypoxic and ischemic central nervous system disorders in infants and children. Adv. Pediatr. 42 (1995) 1-45
Kataoka K., and Yanase H. Mild hypothermia-A revived countermeasure against ischemic neuronal damages. Neurosci. Res. 32 (1998) 103-117
Krieger D.W., and Yenari M.A. Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us?. Stroke 35 (2004) 1482-1489
Ling E.A. Transformation of monocytes into amoeboid microglia in the corpus callosum of postnatal rats, as shown by labelling monocytes by carbon particles. J. Anat. 128 (1979) 847-858
Ling E.A., and Wong W.C. The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 7 (1993) 9-18
Maffei C.M., Mirels L.F., Sobel R.A., Clemons K.V., and Stevens D.A. Cytokine and inducible nitric oxide synthase mRNA expression during experimental murine cryptococcal meningoencephalitis. Infect. Immun. 72 (2004) 2338-2349
McRae A., Gilland E., Bona E., and Hagberg H. Microglia activation after neonatal hypoxic-ischemia. Brain Res. Dev. Brain Res. 84 (1995) 245-252
Menge T., Jander S., and Stoll G. Induction of the proinflammatory cytokine interleukin-18 by axonal injury. J. Neurosci. Res. 65 (2001) 332-339
Mori I., Hossain M.J., Takeda K., Okamura H., Imai Y., Kohsaka S., and Kimura Y. Impaired microglial activation in the brain of IL-18-gene-disrupted mice after neurovirulent influenza A virus infection. Virology 287 (2001) 163-170
Nakajima K., and Kohsaka S. Microglia: activation and their significance in the central nervous system. J. Biochem. (Tokyo) 130 (2001) 169-175
Okamura H., Tsutsi H., Komatsu T., Yutsudo M., Hakura A., Tanimoto T., Torigoe K., Okura T., Nukada Y., Hattori K., et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378 (1995) 88-91
Relton J.K., and Rothwell N.J. Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Res. Bull. 29 (1992) 243-246
Rice III J.E., Vannucci R.C., and Brierley J.B. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann. Neurol. 9 (1981) 131-141
Rothwell N., Allan S., and Toulmond S. The role of interleukin 1 in acute neurodegeneration and stroke: pathophysiological and therapeutic implications. J. Clin. Invest. 100 (1997) 2648-2652
Schmidt O.I., Morganti-Kossmann M.C., Heyde C.E., Perez D., Yatsiv I., Shohami E., Ertel W., and Stahel P.F. Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury. J. Neuroinflammation 1 (2004) 13
Shohami E., Ginis I., and Hallenbeck J.M. Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Factor Rev. 10 (1999) 119-130
Silverstein F.S., Barks J.D., Hagan P., Liu X.H., Ivacko J., and Szaflarski J. Cytokines and perinatal brain injury. Neurochem. Int. 30 (1997) 375-383
Sizonenko S.V., Kiss J.Z., Inder T., Gluckman P.D., and Williams C.E. Distinctive neuropathologic alterations in the deep layers of the parietal cortex after moderate ischemic-hypoxic injury in the P3 immature rat brain. Pediatr. Res. 57 (2005) 865-872
Thoresen M., Bagenholm R., Loberg E.M., Apricena F., and Kjellmer I. Posthypoxic cooling of neonatal rats provides protection against brain injury. Arch. Dis. Child., Fetal. Neonatal. Ed. 74 (1996) F3-F9
Tomimatsu T., Fukuda H., Endo M., Watanabe N., Mu J., Kohzuki M., Fujii E., Kanzaki T., and Murata Y. Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat: phosphorylation of Akt, activation of caspase-3-like protease. Neurosci. Lett. 312 (2001) 21-24
Tomimatsu T., Fukuda H., Endoh M., Mu J., Watanabe N., Kohzuki M., Fujii E., Kanzaki T., Oshima K., Doi K., Kubo T., and Murata Y. Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats. Brain Res. 926 (2002) 108-117
Tomimatsu T., Fukuda H., Endoh M., Mu J., Kanagawa T., Hosono T., Kanzaki T., Doi K., Kubo T., and Murata Y. Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic brain injury in rats, assessed by auditory brainstem response. Pediatr. Res. 53 (2003) 57-61
Touzani O., Boutin H., Chuquet J., and Rothwell N. Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. J. Neuroimmunol. 100 (1999) 203-215
Wang X., Louden C., Yue T.L., Ellison J.A., Barone F.C., Solleveld H.A., and Feuerstein G.Z. Delayed expression of osteopontin after focal stroke in the rat. J. Neurosci. 18 (1998) 2075-2083
Wheeler R.D., Boutin H., Touzani O., Luheshi G.N., Takeda K., and Rothwell N.J. No role for interleukin-18 in acute murine stroke-induced brain injury. J. Cereb. Blood Flow Metab. 23 (2003) 531-535
Wheeler R.D., Brough D., Le Feuvre R.A., Takeda K., Iwakura Y., Luheshi G.N., and Rothwell N.J. Interleukin-18 induces expression and release of cytokines from murine glial cells: interactions with interleukin-1 beta. J. Neurochem. 85 (2003) 1412-1420
Yatsiv I., Morganti-Kossmann M.C., Perez D., Dinarello C.A., Novick D., Rubinstein M., Otto V.I., Rancan M., Kossmann T., Redaelli C.A., Trentz O., Shohami E., and Stahel P.F. Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury. J. Cereb. Blood Flow Metab. 22 (2002) 971-978
Zhu C., Wang X., Cheng X., Qiu L., Xu F., Simbruner G., and Blomgren K. Post-ischemic hypothermia-induced tissue protection and diminished apoptosis after neonatal cerebral hypoxia-ischemia. Brain Res. 996 (2004) 67-75
