Commentary Brief update on hemodynamic responses in animal models of neonatal stroke and hypoxia–ischemia ☆ C. Charriaut-Marlangue a, ⁎, P. Bonnin b,c , P.L. Leger a,d , S. Renolleau d a Univ Paris Diderot, Sorbonne Paris Cité, INSERM, U676, 75019 Paris, France b Univ Paris Diderot, Sorbonne Paris Cité, INSERM, U965, 75010 Paris, France c Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Lariboisière, Physiologie Clinique, Explorations-Fonctionnelles, 75010 Paris, France d UPMC-Paris6, AP-HP, Hôpital Armand Trousseau, Service de Réanimation Néonatale et Pédiatrique, 75012 Paris, France article info Article history: Received 19 June 2013 Accepted 25 June 2013 Available online 2 July 2013 Perinatal arterial stroke is a cerebrovascular event occurring around the time of birth, with pathological or radiological evidence of focal arterial infarction mainly affecting the middle cerebral arterial territory, with an incidence of 1 in 2500 term births (Badve et al., 2012). Perinatal hypoxia–ischemia (HI) is a major cause of acute mor- tality, with an incidence of 2–4 per 1000 full term births (Vannucci, 2000). Perinatal brain injury induced by stroke and/or HI has been as- sociated with permanent neuropsychological handicaps, including mental retardation, cerebral palsy, epilepsy or learning disability. No therapeutic method is available for perinatal encephalopathy apart from initiating hypothermia within 6 h after birth, but only 1 infant in 6 benefits (Azzopardi et al., 2009; Gonzalez and Ferriero, 2009). Although these studies provide proof of concept that in this context cell death is both delayed and preventable, the protection is limited and there is still no treatment available for perinatal stroke or brain injury occurring in preterm and term infants. Clinical presentations (cause, severity, magnitude, and deteriorating speed), and inherent potentials (adaptation, preconditioning-tolerance, and intolerance) against an HI or ischemic insult are different from one infant to anoth- er. Consequently, it is incumbent on scientists in the field of neonatal brain injury to address the questions of therapeutic efficacy of an array of potential therapies in several developmentally appropriate models. Towards that end, a number of new models of neonatal HI and stroke have been introduced recently, the last being that reported by Tsuji et al. (2013). These models have been designed in the rat and mouse brain and most of them present a great variability in the lesion size and brain areas damaged, whereas this last reported model in the mouse is highly reproducible with a selective cortical infarction. Experimental Neurology 248 (2013) 316–320 ☆ The authors declare no conflict of interest. ⁎ Corresponding author at: INSERM, U676, Hopital Robert Debré, 48 Bd Serurier, 75019 Paris, France. Fax: +33 1 40 03 19 95. E-mail address: christiane.marlangue@gmail.com (C. Charriaut-Marlangue). Variability between models can basically be the result of the developmental stage of the animal used, and hemodynamic status of the brain in one specific species at one specific age. In the following commentary we aim to address the impact of ischemic and/or hypoxic injury on the collateral network leading to its recruitment or failure during and/or after injury in the rat and mouse brain. Collateral circu- lation is now recognized to be a potent prognostic factor and suggested to harness potential therapeutic advances from acute stroke to chronic cerebrovascular diseases (Liebeskind, 2012). Through the use of 2D color-coded pulsed Doppler ultrasound and laser speckle contrast im- aging, the state of spatiotemporal profiles of cerebral blood-flow (CBF) changes in large arteries and cortical microvessels respectively, can now be measured and characterized. Species differences Classic studies that established neurodevelopmental parallels across species (Clancy et al., 2001; Dobbing and Sands, 1979) have provided the foundation for the use of animal models to study injury in the developing brain. Recent multivariate analysis of aspects of more than 100 neurodevelopmental events has provided a useful tool for comparing the prenatal and early postnatal brain develop- ment of ten mammalian species with that of the human (Clancy et al., 2007) associated with a web site (http://translatingtime.net/). Using these data, there is now compelling evidence that the postnatal 7-day-old rat (P7), in many ways has brain maturity equivalent to that of an early third trimester human fetus (Clancy et al., 2001, 2007). At this specific age, animals do not open eyes, whereas eyelid opening was observed in older rat and mouse at P14 and P12, respec- tively. Models using P12 mouse and P14 rat can be then more repre- sentative of full-term babies. The brain vasculature undergoes extensive endothelial proliferation and branching in the first postna- tal month. A plateau of cortical vessel branching is observed between P15 and P25 while endothelial cell proliferation peaks around P10 (Harb et al., 2013), and vascular density increases between P8 and P21 (Fernandez-Lopez et al., 2013). Thus, changes in postnatal micro- vasculature during development may also play a key role in response to ischemic and/or hypoxic–schemic injury. Across a wide range of species, two carotid and two vertebral ar- teries supply blood flow to the brain. However, the relative contribu- tion of these large conductance vessels is highly variable (Purves, Please cite this article as: Charriaut-Marlangue, C., et al., Brief update on hemodynamic responses in animal models of neonatal stroke and hypoxia–ischemia, Exp. Neurol. (2013), http://dx.doi.org/10.1016/j.expneurol.2013.06.022 0014-4886/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.expneurol.2013.06.022 Contents lists available at SciVerse ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr