Journal of N euroscience Methods, 35 (1990) 253-260 253 Elsevier NSM 01160 Evaluation of brain damage in a rat model of neonatal hypoxic-ischemia P. Andin6 1, M. Thordstein 2, I. Kjellmer 2,3, C. Nordborg 4, K. Thiringer 2.3, E. Wennberg 5 and H. Hagberg 1,6 1 Institute of Neurobiology, : Department of Physiology, ~ Department of Pediatrics L 4 Department of Pathology and ~ Department of Anesthesiology, University of G6teborg, GOteborg (Sweden), 6 Department of Gynecology and Obstetrics, Bordls Hospital Bordzs (Sweden) (Received 13 December 1989) (Revised version received 10 April and 16 July 1990) (Accepted 20 July 1990) Kev words: Neonatal; Asphyxia; Hypoxia; Ischemia; Somatosensory evoked potentials In spite of improvements in obstetric and neonatal care, hypoxic-ischemic brain damage with severe neurologic disability is still a clinical reality. A model in 7-day-old rats has been introduced to study the pathophysiology of perinatal hypoxic-ischemic brain damage. Unilateral brain damage is produced in the cerebral cortex, striatum and hippocampus, i.e. a similar distribution as is often seen in human asphyxiated neonates. In the present investigation the model was evaluated further by comparing three different methods to assess the brain damage: weighing the hemispheres, morphometry and somatosensory evoked potentials. Seven-day-old rats were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (7.7% 02 at 36 ° C). After 2 h of hypoxic-ischemia pCO 2 and pO 2 decreased in mixed arterial/venous blood. The evaluation of the damage 2 weeks after the insult, demonstrated close correlation between morphometry and weighing (r = 0.836, P < 0.01). The amplitude of evoked potentials correlated to the other parameters (r = 0.814, P < 0.01 and r = 0.824, P'< 0.01 respectively) and displayed a greater relative attenuation than the other methods but with a more pronounced variability. These results indicate that the degree of brain damage can be assessed by weighing for screening purposes.. Introduction Intrauterine hypoxia and intrapartum asphyxia constitute significant risk factors for neurologic disability in the infant (Hagberg and Hagberg, 1984; Soothill et al., 1987; Blair and Stanley, 1988). Several animal models have been used to study the immature brain during hypoxic insults (Myers 1975; Myers 1977; Ros6n et al., 1986; Ment et al. 1987). Most of these models are com- plicated, expensive and difficult to use for screen- ing purposes. The neonatal rat model used in the present Correspondence." P. Andin6, Institute of Neurobiology, Univer- sity of G6teborg, P.O. Box 33031, S-400 33 GOteborg, Sweden. study is a modified Levine preparation, i.e. the carotid artery is ligated unilaterally and the rats are exposed to 1.5-3 h of hypoxia (8% 02) (Levine. 1960; Rice et al., 1981; Dwyer et al., 1988). The cerebral blood flow and the content of ATP and glucose in the hemisphere ipsilateral to the liga- tion decrease and reach very low levels at the end of the hypoxic-ischemia in the parietal and frontal cortex, thalamus and striatum, whereas the con- tralateral hemisphere, the brainstem and cerebel- lum are not ischemic (Welsh et al,, 1982; Silver- stein et al., 1984; Vannucci et al., 1987, 1988). The rats survive for weeks to months and develop brain damage in several brain regions (Rice et al., 1981). This model has been used to assess the potency of putatively neuroprotective agents (Silverstein et al., 1986; McDonald et al., 1987: 0165-0270/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)