Elsevier

Behavioural Brain Research

Volume 157, Issue 1, 10 February 2005, Pages 157-165
Behavioural Brain Research

Research report
Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic–ischemic injury

https://doi.org/10.1016/j.bbr.2004.06.019Get rights and content

Abstract

Severe perinatal hypoxia–ischemia is an important cause of brain injury in both full-term and premature newborns, with a high risk of future behavioral and neurological deficits. The most commonly used animal model of neonatal hypoxia–ischemia is the unilateral ligation of the common carotid artery followed by exposure to hypoxia in 7-day-old rats. In spite of the wide use of this model, lot of contradictions and discrepancies exist between the results obtained by different laboratories regarding behavioral deficits and there are no data regarding the possible delay of the appearance of neurological reflexes and the time-course of reflex performances following neonatal hypoxic–ischemic injury in rats. In the present study we showed that neonatal hypoxia–ischemia retarded the development of somatic growth and several neurological reflexes (ear twitch, grasping, gait and negative geotaxis). Hypoxic animals also displayed retarded performance in righting, geotaxis and gait reflexes. Although hypoxic pups performed worse in most tests for motor coordination, they reached normal levels by 5 weeks of age except in the footfault test. In the open-field, hypoxic animals were generally more active, except at 3 weeks, when activity of normal pups increased enormously as well. Brain areas were significantly reduced in hypoxic animals, but no close correlation was found with behavioral deficits.

Introduction

Perinatal hypoxic–ischemic injury is a serious problem in both full-term and premature human neonates, with a high risk of future behavioral and neurological deficits. In spite of improvements in obstetric and neonatal intensive care, hypoxic–ischemic brain damage with severe neurological disability remains a clinical problem and studies in animal models continue to be of high demand [2]. The most commonly used rodent model of neonatal hypoxia–ischemia is the unilateral ligation of the carotid artery followed by a period of hypoxic exposure. Locomotor ability, learning and memory deficits have been described in juvenile and adult rats subjected to a hypoxic–ischemic insult in the perinatal period.

Postnatal development is reflected among others by the maturation of neurological reflexes and motor coordination. The appearance of certain neurological reflexes is known to be influenced by various factors [21], [38], [39]. Although the maturation of neurological reflexes represents hallmarks of nervous system development [1], [15], [18], [21], [38], [39], relatively little is known about the maturation of these reflexes following neonatal hypoxic–ischemic injury. In a recent study, a selected set of neurological reflexes has been examined 1 and 24 h after the hypoxic insult in neonatal mice [40]. Short-term neurofunctional outcome as measured by the righting reflex, cliff aversion and geotaxis closely correlated with long-term functional deficits measured by water-maze test [40]. This study draws the attention to the predictive value and necessity of short-term functional evaluation. Therefore, the primary aim of the present study was to examine the development of neurological reflexes in rats subjected to neonatal hypoxic–schemic injury. Tests of motor coordination and open-field behavior are frequently used in studies with neonatal hypoxia, but results are often contradictory. Therefore, besides examining reflexes, we also investigated the performance of hypoxic rats in several motor coordination tasks as well as in the open-field.

Section snippets

Animals

Litters of Wistar rats (10 ± 2) were used. Whole litters were used in order to avoid effects of sexual isolation [17]. It has been reported previously that sex does not influence the appearance of reflexes nor the extent of brain damage after hypoxia–ischemia [30], [45], therefore, both male and female pups were used in our experiments. Animals were maintained under 12 h light/dark cycle with free access to food and water. Pups were weaned after 3 weeks of age. Animal housing, care and

Results

Only two hypoxic–ischemic pups died during the first 24 h after the insult, and 1 further pup died during the 3rd postoperative week. No animal died in the control group. Due to the short operational procedure, no animal had to be excluded due to changes in the temperature. Retardation of somatic development was reflected in significantly less weight gain in hypoxic animals throughout the observation period (Fig. 1). Although pups with the same average birth weight were used (not shown), body

Discussion

In the present study we showed that an approximately 50% atrophy of the hypoxic hemisphere results in retarded neurobehavioral development as shown by delayed appearance and worse performance of some neurological reflexes, and retarded development of motor coordination. However, in spite of the permanent cerebral atrophy, most animal reached control levels by 6 weeks of age in most tests, except for the footfault test. In the open-field, hypoxic animals were more active at 2 and 6 weeks of age.

Acknowledgements

This work was supported by the Hungarian National Scientific Research Fund (OTKA T 034491, T046589), the Hungarian Academy of Sciences and Bolyai Scholarship.

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