Auditory processing deficits in rats with neonatal hypoxic-ischemic injury Melissa M. McClure a , Ann M. Peiffer a , Glenn D. Rosen b , R. Holly Fitch a, * a Department of Psychology, Behavioral Neuroscience Division, Unit 4154, 3107 Horse Barn Hill Rd., Storrs, CT 06269-4154, USA b Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Received 7 June 2004; received in revised form 30 November 2004; accepted 1 December 2004 Abstract Hypoxia-ischemia (HI) refers to reduced blood oxygenation and/or a diminished amount of blood perfusing the brain, and is associated with premature birth/very low birth weight (VLBW). HI represents a common cause of injury to the perinatal brain. Indeed, a significant number of premature/VLBW infants go on to demonstrate cognitive/behavioral deficits, with particularly high incidence of disruptions in language development. Auditory processing deficits, in turn, have been suggested to play a causal role in the development of language impairments. Specifically, the inability to identify fast elements in speech is purported to exert cascading detrimental effects on phonological discrimination, processing, and identification. Based on this convergent evidence, the current studies address auditory processing evaluation in a rodent model of HI injury induced on postnatal days 1, 7, or 10 (which in turn is well accepted as modeling HI-related injury to the perinatal human). Induced injuries were followed by a battery of auditory testing, and a spatial maze assessment, performed both during juvenile and adult periods. Results indicate that rats suffering from these early HI insults performed significantly worse than shams on tasks requiring rapid auditory processing, and on a test of spatial learning (Morris water maze (MWM)), although these effects were not seen on simpler versions of auditory tasks or on a water escape assessment (thus ruling out hearing/motor impairments). Correlations were found between performance on rapid auditory and spatial behavioral tasks and neuroanatomical measures for HI animals such as: the volume of the hippocampus, cerebral cortex, ventricles, and/or the area of the corpus callosum. Cumulative findings suggest that perinatal HI injury in the rat may lead to neurodevelopmental damage associated, in turn, with auditory processing and/or learning and memory impairments. As such, the current model may have critical implications for the study of neurophysiological underpinnings of cognitive deficits in premature/VLBW infants. # 2004 ISDN. Published by Elsevier Ltd. All rights reserved. Keywords: Hypoxia-ischemia; Very low birth weight (VLBW); Morris water maze; Auditory; Prematurity; Language deficit 1. Introduction Hypoxia/ischemia (HI), or a reduction in blood oxygena- tion and flow, represents a common cause of damage to the perinatal brain, and can occur via different etiologies (Vannucci, 2000). In premature infants, damage consistent with HI is associated with the rupture of blood vessels (often in the vascular bed of the subependymal matrix), which can produce tissue compression, disruption of cerebrospinal fluid flow, and dilation of the ventricles (Volpe, 2001). In term infants, HI injury is often associated with asphyxia, placental dysfunction, and prolonged labor and/or resuscita- tion. HI resulting from premature birth is also associated with lower than average birth weights. A significant percentage (approximately 10%) of very low birth weight infants (VLBW, <1500 g) go on to exhibit gross motor deficits such as cerebral palsy, and an even greater percentage (25–50%) go on to demonstrate cognitive and other behavioral deficits (Volpe, 2001). Some examples of these deficits include: hearing impairment and/or speech problems (Kenworthy et al., 1987); delayed language development (Vohr et al., 1988; Casiro et al., 1990); low IQ (Ross et al., 1985); and deficits in phonological short- term memory (Briscoe et al., 1998). Auditory processing deficits have also been reported in premature babies, and such deficits have been suggested to play a causal role in the development of language related impairments in this www.elsevier.com/locate/ijdevneu Int. J. Devl Neuroscience 23 (2005) 351–362 * Corresponding author. Tel.: +1 860 486 2554; fax: +1 860 486 3827. E-mail address: Roslyn.h.fitch@uconn.edu (R.H. Fitch). 0736-5748/$30.00 # 2004 ISDN. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijdevneu.2004.12.008