Maternal intrauterine inflammation has been implicated in the development of periventricular leukomalacia and white matter injury in the neonate. We hypothesized that intrauterine endotoxin administration would lead to microstructural changes in the neonatal rabbit white matter in vivo that could be detected at birth using diffusion tensor magnetic resonance imaging (MRI). Term newborn rabbit kits (gestational age 31 days) born to dams exposed to saline or endotoxin in utero on gestational day 28 underwent diffusion tensor imaging, and brain sections were stained for microglia. Comparison between normal and endotoxin groups showed significant decreases in both fractional anisotropy and eigenvalue (e1) in all periventricular white matter regions that showed an increase in the number of activated microglial cells, indicating that after maternal inflammation, microglial infiltration may predominantly explain this change in diffusivity in the immediate neonatal period. Diffusion tensor imaging may be a clinically useful tool for detecting neuroinflammation induced by maternal infection in neonatal white matter.
Dammann O., Leviton A.Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res. 1997;42(1):1-8.
2.
Goepfert AR, Andrews WW, Carlo W., et al. Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of neonatal morbidity. Am J Obstet Gynecol . 2004;191(4):1375-1381.
3.
Heep A., Behrendt D., Nitsch P., Fimmers R., Bartmann P., Dembinski J.Increased serum levels of interleukin 6 are associated with severe intraventricular haemorrhage in extremely premature infants. Arch Dis Child Fetal Neonatal Ed. 2003; 88(6):501-504.
4.
Nelson KB, Dambrosia JM, Grether JK, Phillips TMNeonatal cytokines and coagulation factors in children with cerebral palsy . Ann Neurol. 1998;44(4):665-675.
5.
Viscardi RM, Muhumuza CK, Rodriguez A., et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res. 2004; 55(6):1009-1017.
6.
Yoon BH, Jun JK, Romero R., et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol. 1997;177(1):19-26.
7.
Yoon BH, Romero R., Park JSFetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol. 2000;182(3): 657-681.
8.
Cioni G., Di Paco MC, Bertuccelli B., Paolicelli PB, Canapicchi R.MRI findings and sensoriomotor development in infants with bilateral spastic cerebral palsy. Brain Dev. 1997;19(4):245-253.
9.
Hashimoto K. , Hasegawa H., Kida Y., Takeuchi Y.Correlation between neuroimaging and neurological outcome in periventricular leukomaleacia: diagnostic criteria. Pediatr Int. 2001; 43(3):240-245.
10.
Kulak W., Sobaniec W., Kubas B., et al. Spastic cerebral palsy: clinical magnetic resonance imaging correlation of 129 children. J Child Neurol. 2007;22(1):8-14.
11.
Kwong KL, Wong YC, Fong CM, Wong SN, So KTMagnetic resonance imaging in 122 children with spastic cerebral palsy. Pediatr Neurol. 2004;31(3):172-176.
12.
Lee ZI, Byun WM, Jang SH, Ahn SH, Moon HK, Chang Y.Diffusion tensor magnetic resonance imaging of microstructural abnormalities in children with brain injury. Am J Phys Med Rehabil. 2003;82(7):556-559.
13.
Son SM, Ahn YH, Sakong J., et al. Diffusion tensor imaging demonstrates focal lesions of the corticospinal tract in hemiparetic patients with cerebral palsy. Neurosci Lett. 2007; 420(1):34-38.
Fan GG, Yu B., Quan SM, Sun BH, Guo QYPotential of diffusion tensor MRI in the assessment of periventricular leukomalacia . Clin Radiol. 2006;61(4):358-364.
16.
Neil J., Miller J., Mukherjee P., Hüppi PSDiffusion tensor imaging of normal and injured developing human brain-a technical review. NMR Biomed. 2002;15(7-8):543-552.
17.
Drobyshevsky A., Bregman J., Storey P., et al. Serial diffusion tensor imaging detects white matter changes that correlate with motor outcome in premature infants . Dev Neurosci. 2007; 29(4-5):289-301.
18.
Åden U., Dahlberg V., Fredholm BB, Lai LJ, Chen Z., Bjelke B.MRI Evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice. Stroke . 2002;33(5): 1405-1410.
19.
Rumpel H., Nedelcu J., Aguzzi A., Martin E.Late glial Swelling after acute cerebral hypoxia-ischemia in the neonatal rat: a combined magnetic resonance and histochemical study. Pediatr Res. 1997;42(1):54-59.
20.
Drobyshevsky A., Derrick M., Wyrwicz AM, et al. White matter injury correlates with hypertonia in an animal model of cerebral palsy. J Cereb Blood Flow Metab. 2007;27(2):270-281.
21.
Kannan S., Saadani-Makki F., Muzik O., et al. Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: detection with 11C-(R)-PK11195 and small-animal PET. J Nucl Med.2007;48(6):946-954.
22.
Saadani-Makki F., Kannan S., Lu X., et al. Intrauterine administration of endotoxin leads to motor deficits in a rabbit model: a link between prenatal infection and cerebral palsy. Am J Obstet Gynecol.2008 ;199(6):651-657.
23.
Jiang H., van Zijl PC, Kim J., Pearlson GD, Mori S.DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking. Comput Methods Programs Biomed. 2006; 81(2):106-116.
24.
Ulfig N., Nickel J., Bohl J.Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain. Cell Tissue Res. 1998; 291(3):433-443.
25.
Sun SW, Liang HF, Schmidt RE, Cross AH, Song SKSelective vulnerability of cerebral white matter in a murine model of multiple sclerosis detected using diffusion tensor imaging. Neurobiol Dis. 2007;28(1):30-38.
26.
Budde MD, Kim JH, Liang HF, et al. Toward accurate diagnosis of white matter pathology using diffusion tensor imaging. Magn Reson Med. 2007;57(4):688-695.
27.
Kim JH, Loy DN, Liang HF, Trinkaus K., Schmidt RE, Song SKNoninvasive diffusion tensor imaging of evolving white matter pathology in a mouse model of acute spinal cord injury. Magn Reson Med . 2007;58(2):253-260.
28.
Sun SW, Liang HF, Cross AH, Song SKEvolving Wallerian degeneration after transient retinal ischemia in mice characterized by diffusion tensor imaging. NeuroImage. 2008 ;40(1): 1-10.
29.
Sun SW, Liang HF, Le TQ, Armstrong RC, Cross AH, Song SKDifferential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia. NeuroImage. 2006;32(3):1195-1204.
30.
Song SK, Yoshino J., Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. NeuroImage. 2005;26(1):132-140.
31.
Sun SW, Liang HF, Trinkaus K., Cross AH, Armstrong RC, Song SKNoninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum. Magn Reson Med. 2006;55(2):302-308.
32.
Beaulieu C.The basis of anisotropic water diffusion in the nervous system-a technical review. NMR Biomed. 2002;15(7-8): 435-455.
33.
Harsan LA, Poulet P., Guignard B., Parizel N., Skoff RP, Ghandour MSAstrocytic hypertrophy in dysmyelination influences the diffusion anisotropy of white matter. J Neurosci Res. 2007;85(5):935-944.
34.
Nakane M., Tamura A., Miyasaka N., Nagaoka T., Kuroiwa T.Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the middle cerebral artery in rats. AJNR Am J Neuroradiol . 2001;22(4):660-663.
35.
Hervé D., Molko N., Pappata S., et al. Longitudinal thalamic diffusion changes after middle cerebral artery infarcts. J Neurol Neurosurg Psychiatry. 2005;76(2):200-205.
36.
Drobyshevsky A., Song SK, Gamkrelidze G., et al. Developmental changes in diffusion anisotropy coincide with immature oligodendrocyte progression and maturation of compound action potential. J Neurosci. 2005;25(25):5988-5997.
37.
Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HCLate oligodendrocytes progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci . 2001;21(4): 1302-1312.
38.
Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci. 2002;22(2):455-463.
39.
Bass WT, Singer GA, Liuzzi FJTransient lectin binding by white matter tract border zone microglia in the foetal rabbit brain. Histochem J. 1998;30(9):657-666.
40.
de Graaf-Peters VB, Hadders-Algra M.Ontogeny of the human central nervous system: What is happening when?Early Hum Dev. 2006 ;82(4):257-266.
41.
Fields RDMyelination: an overlooked mechanism of synaptic plasticity? Neuroscientist. 2005;11(6):528-531.
42.
Valsasina P. , Agosta F., Benedetti B., et al. Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis . J Neurol Neurosurg Psychiatry. 2007; 78(5):480-484.
43.
Malik GK, Trivedi R., Gupta A., Singh R., Prasad KN, Gupta RK. Quantitative DTI assessment of periventricular white matter in neonatal meningitis. Brain Dev. 2008;30(5):334-341.
44.
Allen IV, McKeown SRA histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci. 1979;41(1):81-91.
45.
Neusch C., Bähr M., Schneider-Gold C.Glia cells in amyotrophic lateral sclerosis: new clues to understanding an old disease?Muscle Nerve.2007;35(6):712-724.
46.
Nau R., Brück W.Neuronal injury in bacterial meningitis; mechanisms and implications for therapy . Trends Neurosci. 2002;25(1):38-45.
47.
Arzoumanian Y., Mirmiran M., Barnes PD, et al. Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth preterm infants. AJNR Am J Neuroradiol. 2003;24(8):1646-1653.
48.
Thomas B., Eyssen M., Peeters R., et al. Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury. Brain. 2005;128(pt 11):2562-2577.
49.
Ward P., Counsell S., Allsop J., et al. Reduced fractional anisotropy on diffusion tensor magnetic resonance imaging after hypoxic-ischemic encephalopathy. Pediatrics . 2006;117(4): 619-630.
50.
Murakami A. , Morimoto M., Yamada K., et al. Fiber tracking techniques can predict the degree of neurologic impairment for periventricular leukomalacia. Pediatrics. 2008;122(3): 500-506.
51.
Herber DL, Maloney JL, Roth LM, Freeman MJ, Morgan D., Gordon MNDiverse microglial responses after intrahippocampal administration of lipopolysaccharide . Glia. 200;53(4): 382-391.
