Neonatal cerebral hypoxia-ischemia causes lateralized memory impairments in the adult rat

Neonatal hypoxia-ischemia (HI) has been extensively studied in a rat model characterized by unilateral brain damage (Rice-Vannucci Model). However, as well as in humans, each rat brain hemisphere is distinctly involved in cognitive functions, as for example retrieval of emotionally based memory, and neurochemical asymmetries have been described. In this paper we investigated whether hypoxia-ischemia could cause distinct cognitive deficits depending on which hemisphere is damaged. Seven-day-old male Wistar rats were submitted to permanent occlusion of left or right common carotid artery and were exposed to a mixture of 8% oxygen-92% nitrogen for 2.5 h. On adulthood, these rats were trained in step-down inhibitory avoidance and in two tasks in the Morris water maze. Both experimental groups (right and left lesioned) showed a deficit of retrieval in the inhibitory avoidance task compared to controls, although rats with right hemisphere lesion showed a significantly greater deficit than the left damaged group (P<0.05). In the Morris maze, both damaged groups presented cognitive deficits in the reference memory task (P<0.05), however only the right damaged group had an impairment in the working memory task. Brain coronal areas, at levels +1.20 and -3.30 mm from bregma of both HI groups were smaller than those of control, with no differences between the right and left damaged groups (P<0.05). These results show that cerebral hypoxia-ischemia in neonatal rats causes asymmetric behavioral outcomes depending on which of the hemispheres is lesioned and support the hypothesis of lateralization of cognitive functions in the rodent brain.