Abstract
We investigated whether the changes detectable with magnetic resonance imaging techniques during and after an episode of cerebral hypoxia-ischemia differ in immature and older brain. Diffusion weighted (DW) and T2-weighted (T2W) images were repeatedly acquired before, during, and after an episode of cerebral hypoxia-ischemia (unilateral carotid artery occlusion plus hypoxia) in 2- and 4-wk-old rats lightly anesthetized with isoflurane. Areas of increased brightness were detected in DW images from both 2- and 4-wk-old rats by 10-20 min after the start of hypoxia. These hyperintense areas increased during hypoxia, comprising 60.8 ± 4.9% and 30.5 ± 2.7% of the brain image at the level of the thalamus in 2-wk-old and 4-wk-old animals, respectively (p < 0.003). Hyperintense areas (e.g. 27.0 ± 8.3%) also appeared in T2W images during hypoxia-ischemia in 2-wk-old animals, but these did not occur in 4-wk-old animals (p < 0.02). This observation was reflected in T2, which increased during hypoxia-ischemia in the 2-wk-old but not the 4-wk-old group. By 60 min after the termination of hypoxia-ischemia in either age group, areas of hyperintensity resolved and then reappeared 24 h later on both DW and T2W images. Thus, irrespective of age, magnetic resonance imaging changes during transient hypoxia-ischemia generally recover with a delayed or secondary increase in DW and T2W hyperintensity hours later. Immature brain differs from older brain primarily with respect to some combination of hypoxic/ischemic cellular or biochemical changes, that are detectable as increases in T2 within 2-wk-old but not 4-wk-old animals.
Similar content being viewed by others

Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- DW:
-
diffusion-weighted
- T2W:
-
T2-weighted
- MR:
-
magnetic resonance
- TR:
-
repetition time
- TE:
-
echo time
References
Mintorovitch J, Yang GY, Shimizu H, Kucharczyk J, Chan PH, Weinstein PR 1994 Diffusion-weighted magnetic resonance imaging of acute focal cerebral ischemia: comparison of signal intensity with changes in brain water and Na+, K+-ATPase activity. J Cereb Blood Flow Metab 14: 332–336
Van Bruggen N, Roberts TPL, Cremer JE 1994 The application of magnetic resonance imaging to the study of experimental cerebral ischaemia. Cerebovasc Brain Metab Rev 6: 180–210
Le Bihan D, Turner R, Douek P, Patronas N 1992 Diffusion MR imaging: clinical applications. AJR Am J Roentgenol 159: 591–599
Moseley ME, Cohen Y, Mintorovitch J, Chileuitt L, Shimizu H, Kucharczyk J, Wendland MF, Weinstein PR 1990 Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med 14: 330–346
Hossmann KA, Hoehn-Berlage M 1995 Diffusion and perfusion MR imaging of cerebral ischemia. Cerebrovasc Brain Metab Rev 7: 187–217
Mancuso A, Karibe H, Rooney WD, Zarow GJ, Graham SH, Weiner MW, Weinstein PR 1995 Correlation of early reduction in the apparent diffusion coefficient of water with blood flow reduction during middle cerebral artery occlusion in rats. Magn Reson Med 34: 368–377
Welch KMA, Windham J, Knight RA, Nagesh V, Hugg JW, Jacobs M, Peck D, Booker P, Dereski MO, Levine SR 1995 A model to predict the histopathology of human stroke using diffusion- and T-2-weighted magnetic resonance imaging. Stroke 26: 1983–1989
Lutsep HL, Albers GW, Decrespigny A, Kamat GN, Marks MP, Moseley ME. 1997 Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke. Ann Neurol 41: 574–580
Vannucci RC 1995 Perinatal hypoxic-ischemic encephalopathy. Neurologist 1: 35–52
Volpe JJ 1992 Brain injury in the premature infant: current concepts of pathogenesis and prevention. Biol Neonate 62: 231–242
Tuor UI, Del Bigio MR, Chumas PD 1996 Brain damage due to cerebral hypoxia-ischemia in the neonate: pathology and pharmacologic modification. Cerebrovasc Brain Metab Rev 8: 159–193
Duffy TE, Kohle SJ, Vannucci RC 1975 Carbohydrate and energy metabolism in perinatal rat brain: relation to survival in anoxia. J Neurochem 24: 271–276
Grafe MR 1994 Developmental changes in the sensitivity of the neonatal rat brain to hypoxic/ischemic injury. Brain Res 653: 161–166
Kusumoto M, Arai H, Mori K, Sato K 1995 Resistance to cerebral ischemia to developing gerbils. J Cereb Blood Flow Metab 15: 886–891
Soriano MA, Tortosa A, Planas AM, Rodriguez-Farré E, Ferrer I 1994 Induction of HSP70 mRNA and HSP70 protein in the hippocampus of the developing gerbil following transient forebrain ischemia. Brain Res 653: 191–198
Yager JY, Shuaib A, Thornhill J 1996 The effect of age on susceptibility to brain damage in a model of global hemispheric hypoxia-ischemia. Brain Res Dev Brain Res 93: 143–154
Tuor UI, Kozlowski P, Del Bigio MR, Ramjiawan B, Su S, Malisza K, Saunders JK 1998 Diffusion and T2 weighted increases in magnetic resonance images of immature brain during hypoxia-ischemia: transient reversal post-hypoxia. Exp Neurol 150: 321–328
Tuor UI, Chumas PD, Del Bigio MR 1995 Prevention of hypoxic-ischemic damage with dexamethasone is dependent on age and not influenced by fasting. Exp Neurol 132: 116–122
Towfighi J, Mauger D, Vannucci RC, Vannucci SJ 1997 Influence of age on the cerebral lesions in an immature rat model of cerebral hypoxia-ischemia: a light microscopic study. Brain Res Dev Brain Res 100: 149–160
Stejskal EO, Tanner JE 1965 Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys 42: 288–292
Miot-Noirault E, Barantin L, Akoka S, Le PA 1997 T2 relaxation time as a marker of brain myelination: experimental MR study in two neonatal animal models. J Neurosci Methods 72: 5–14
Reith W, Hasegawa Y, Latour LL, Dardzinski BJ, Sotak CH, Fisher M 1995 Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat stroke model. Neurology 45: 172–177
Thurston JH, McDougal DB Jr 1969 Effect of ischemia on metabolism of the brain of the newborn mouse. Am J Physiol 216: 348–352
Kass IS, Lipton P 1989 Protection of hippocampal slices from young rats against anoxic transmission damage is due to better maintenance of ATP. J Physiol 413: 1–11
Yager JY, Kala G, Hertz L, Juurlink BHJ 1994 Correlation between content of high-energy phosphates and hypoxic-ischemic damage in immature and mature astrocytes. Brain Res Dev Brain Res 82: 62–68
Hoehn-Berlage M, Norris DG, Kohno K, Mies G, Leibfritz D, Hossmann KA 1995 Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances. J Cereb Blood Flow Metab 15: 1002–1011
Minematsu K, Li L, Sotak CH, Davis MA, Fisher M 1992 Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging in rats. Stroke 23: 1304–1311
Perez-Trepichio AD, Xue M, Ng TC, Majors AW, Furlan AJ, Awad IA, Jones SC 1995 Sensitivity of magnetic resonance diffusion-weighted imaging and regional relationship between the apparent diffusion coefficient and cerebral blood flow in rat focal cerebral ischemia. Stroke 26: 667–674
Hasegawa Y, Fisher M, Latour LL, Dardzinski BJ, Sotak CH 1994 MRI diffusion mapping of reversible and irreversible ischemic injury in focal brain ischemia. Neurology 44: 1484–1490
Miyabe M, Mori S, Vanzijl PCM, Kirsch JR, Eleff SM, Koehler RC, Traystman RJ 1996 Correlation of the average water diffusion constant with cerebral blood flow and ischemic damage after transient middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab 16: 881–891
Muller TB, Haraldseth O, Jones RA, Sebastiani G, Godtliebsen F, Lindboe CF, Unsgard G 1995 Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion. Stroke 26: 451–458
Blumberg RM, Cady EB, Wigglesworth JS, McKenzie JE, Edwards AD 1997 Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain. Exp Brain Res 113: 130–137
Yager JY, Brucklacher RM, Vannucci RC 1991 Cerebral oxidative metabolism and redox state during hypoxia-ischemia and early recovery in immature rats. Am J Physiol 261: H1102–H1108
Marks KA, Mallard EC, Roberts I, Williams CE, Sirimanne ES, Johnston B, Gluckman PD, Edwards AD 1996 Delayed vasodilation and altered oxygenation after cerebral ischemia in fetal sheep. Pediatr Res 39: 48–54
Zarow GJ, Graham SH, Mintorovitch J, Chen J, Yang GY, Weinstein PR 1995 Diffusion-weighted magnetic resonance imaging during brief focal cerebral ischemia and early reperfusion: evolution of delayed infarction in rats. Neurol Res 17: 449–454
Dijkhuizen RM, Knollema S, van der Worp HB, Ter Horst GJ, de Wildt DJ, Berkelbach van der Sprenkel JW, Tulleken KAF, Nicolay K 1998 Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat: evidence for region-specific sensitivity and delayed damage. Stroke 29: 695–704
Kohno K, Ohta S, Kumon Y, Sakaki S, Okujima S 1995 Early detection of cerebral ischemic lesion using diffusion-weighted MRI. J Comput Assist Tomogr 19: 982–986
Rumpel H, Nedelcu J, Aguzzi A, Martin E 1997 Late glial swelling after acute cerebral hypoxia-ischemia in the neonatal rat: a combined magnetic resonance and histochemical study. Pediatr Res 42: 54–59
Mathur-De-Vre R 1984 Biomedical implications of the relaxation behaviour of water related to NMR imaging. Br J Radiol 57: 955–976
Naruse S, Aoki Y, Takei R, Horikawa Y, Ueda S 1991 Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method. Stroke 22: 61–65
Barnes D, McDonald WI, Johnson G, Tofts PS, Landon DN 1987 Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema. J Neurol Neurosurg Psychiatry 50: 125–133
Tuor UI, Simone C, Bascaramurty S 1992 Local blood-brain barrier in the newborn rabbit: postnatal changes in α-aminoisobutyric acid transfer within medulla, cortex, and selected brain areas. J Neurochem 59: 999–1007
Muramatsu K, Fukuda A, Togari H, Wada Y, Nishino H 1997 Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier. Stroke 28: 2281–2288
Go KG 1997 The normal and pathological physiology of brain water. Adv Tech Stand Neurosurg 23: 47–142
Lu M, Lee MD, Smith BL, Jung JS, Agre P, Berduk MAJ, Merkx G, Russ JPL, Deen PMT 1996 The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain. Proc Natl Acad Sci U S A 93: 10908–10912
King LS, Agre P 1996 Pathophysiology of the aquaporin water channels. Annu Rev Physiol 58: 619–648
Nielsen S, Arnulf-Nagelhus E, Amiry-Moghaddam M, Bourque C, Agre P, Petter-Ottersen O 1997 Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 17: 171–180
Acknowledgements
The authors thank R. Summers and T. Foniok for assistance with the statistical calculations and MR image acquisition, respectively.
Author information
Authors and Affiliations
Additional information
Supported in part by a grant from the Heart and Stroke Foundation of Manitoba.
Rights and permissions
About this article
Cite this article
Ning, G., Malisza, K., Del Bigio, M. et al. Magnetic Resonance Imaging during Cerebral Hypoxia-Ischemia: T2 Increases in 2-Week-Old But Not 4-Week-Old Rats. Pediatr Res 45, 173–179 (1999). https://doi.org/10.1203/00006450-199902000-00003
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199902000-00003

