Effect of the reperfusion after cerebral ischemia in neonatal rats using MRI monitoring Sebastien Fau a,c,1 , Chrystelle Po b,1,2 , Brigitte Gillet b,2 , Stephane Sizonenko d , Jean Mariani a,e , Philippe Meric b,2 , Christiane Charriaut-Marlangue a, ⁎ a Université Pierre et Marie Curie-Paris6, UMR-CNRS 7102, groupe HICD, case 14, 9 quai St-Bernard, Paris, F-75005, France b Laboratoire de RMN Biologique ICSN-CNRS, Avenue de la Terrasse, Gif-sur-Yvette, F-91198, France c Service de Réanimation Néonatale et Pédiatrique, Hôpital Armand Trousseau – APHP, Université Pierre et Marie Curie-Paris6, Paris, F-75012, France d Département de Pédiatrie, Université de Genève, Genève, Suisse e APHP, Hôpital Charles Foix, Unité d’Explorations Fonctionnelles (UEF), Ivry sur Seine, F-94200, France Received 11 June 2007; revised 20 July 2007; accepted 30 August 2007 Available online 15 September 2007 Abstract Cerebral hypoxia–ischemia is an important cause of brain injury in the newborn infant. Our purpose was to study magnetic resonance (MR) imaging changes in P7 rat brains submitted to permanent or reversible ischemia. Ischemia was induced by permanent electro-cauterization of the middle cerebral artery combined with a permanent or a transient (50 min) common carotid artery occlusion. The early events during ischemia and reperfusion were investigated by T2-weighted images (T2WI) at 1 and 3 h and by serial diffusion-weighted images (DWI) during 3 h in a 7 T magnet with a standard weighted diffusion sequence (b = 1282.04 s mm - 2 ) and a SEMS sequence. Within the first hour after MCA occlusion, the T2WI areas of contrast enhancement increased to a mean volume of 12.9 ± 6.4%, a steady state still detected at 3 h after the ischemic onset (10.5 ± 2.5%). Contrast enhancement in DWI increased as soon as 15 min of ischemia in all animals up to 50 min after CCA occlusion. In permanent ischemia, DWI abnormalities volume then increased more slowly from 50 min to 3 h after CCA occlusion (+ 25%, n = 5). In reversible ischemia, the DWI abnormalities volume either moderately decreased and reached a plateau (- 8.4%, n = 4) or dramatically decreased (- 53.0%, n = 3). Both T2WI and DWI evidenced a “patchy” pattern of recovery as also shown on cresyl violet-stained sections. In contrast to the adult, early ischemic injury in P7 rat brains is detected as an increase in hyper-intensities both in T2WI and DWI. Our data indicate that reperfusion is able to block edema evolution after neonatal stroke and that early T2WI and more accurately DWI allow to distinguish between different patterns of injury in reversible ischemia. © 2007 Elsevier Inc. All rights reserved. Keywords: Diffusion-weighted imaging; T2-weighted imaging; Recovery; Reperfusion; Undamaged tissue; P7 rat brain; Ischemia Introduction Hypoxic–ischemic encephalopathy is a major cause of infant mortality and morbidity with long-term neurological sequelae in 25% of the survivors (Ferriero, 2004; Nelson, 2007). Assess- ment of infants with moderate and severe encephalopathy is based on the use of clinical examination and EEG recording, which can be applied within hours after delivery, but also on the use of neuroimaging. Magnetic resonance imaging (MRI) is now increasingly used in full term infants with neonatal ence- phalopathy (Rutherford et al., 2006) and many reports have shown that this imaging technique is by far superior to ultra- sound (Maalouf et al., 2001, Mirmiran et al., 2004; O’Shea et al., 2005) and computed tomography (Blankenberg et al., 2000; Robertson et al., 2003) to describe central nervous system injury. MRI is also of value when timing the onset of the lesion (Cowan et al., 2003). Available online at www.sciencedirect.com Experimental Neurology 208 (2007) 297 – 304 www.elsevier.com/locate/yexnr Abbreviations: CCA, common carotid artery; CCAo, CCA occlusion; CBF, cerebral blood flow; MCA, middle cerebral artery; MCAc, MCA coagulation; DWI, diffusion-weighted imaging. ⁎ Corresponding author. Fax: +33 1 44 27 22 80. E-mail address: Christiane.Marlangue@snv.jussieu.fr (C. Charriaut-Marlangue). 1 The two first authors contributed equally to the work. 2 Member of the Network of Excellence: European Molecular Imaging Laboratories (EMIL LHSC-2004 503569). 0014-4886/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2007.08.021