Blandine Bellot1, Julie Peyronnet-Roux2, Catherine Gire3, Umberto Simeoni4, Laurent Vinay2, Jean-Charles Viemari2. 1. 1] Institut de Neurosciences de la Timone (P3M Team), UMR 7289, CNRS, Aix Marseille Université, Marseille, France [2] Pôle de Médecine et Réanimation Néonatales, Assistance Publique Hôpitaux de Marseille, Marseille, France. 2. Institut de Neurosciences de la Timone (P3M Team), UMR 7289, CNRS, Aix Marseille Université, Marseille, France. 3. Pôle de Médecine et Réanimation Néonatales, Assistance Publique Hôpitaux de Marseille, Marseille, France. 4. 1] Pôle de Médecine et Réanimation Néonatales, Assistance Publique Hôpitaux de Marseille, Marseille, France [2] Aix Marseille Université, Marseille, France.
Abstract
BACKGROUND: Perinatal cerebral hypoxia-ischemia (HI) can lead to severe neurodevelopmental disorders. Studies in humans and animal models mainly focused on cerebral outcomes, and little is known about the mechanisms that may affect the brainstem and the spinal cord. Dysfunctions of neuromodulatory systems, such as the serotonergic (5-HT) projections, critical for the development of neural networks, have been postulated to underlie behavioral and motor deficits, as well as metabolic changes. METHODS: The aim of this study was to investigate brainstem and spinal cord functions by means of plethysmography and sensorimotor tests in a neonatal Rice-Vanucci model of HI in mice. We also evaluated bioaminergic contents in central regions dedicated to the motor control of autonomic functions. RESULTS: Mice with cerebral infarct expressed motor disturbances and had a lower body weight and a decreased respiratory frequency than SHAM, suggesting defects of brainstem neural network involved in the motor control of feeding, suckling, swallowing, and respiration. Moreover, our study revealed changes of monoamine and amino acid contents in the brainstem and the spinal cord of HI mice. CONCLUSION: Our results suggest that monoaminergic neuromodulation plays an important role in the physiopathology of HI brain injury that may represent a good therapeutic target.
BACKGROUND: Perinatal cerebral hypoxia-ischemia (HI) can lead to severe neurodevelopmental disorders. Studies in humans and animal models mainly focused on cerebral outcomes, and little is known about the mechanisms that may affect the brainstem and the spinal cord. Dysfunctions of neuromodulatory systems, such as the serotonergic (5-HT) projections, critical for the development of neural networks, have been postulated to underlie behavioral and motor deficits, as well as metabolic changes. METHODS: The aim of this study was to investigate brainstem and spinal cord functions by means of plethysmography and sensorimotor tests in a neonatal Rice-Vanucci model of HI in mice. We also evaluated bioaminergic contents in central regions dedicated to the motor control of autonomic functions. RESULTS:Mice with cerebral infarct expressed motor disturbances and had a lower body weight and a decreased respiratory frequency than SHAM, suggesting defects of brainstem neural network involved in the motor control of feeding, suckling, swallowing, and respiration. Moreover, our study revealed changes of monoamine and amino acid contents in the brainstem and the spinal cord of HI mice. CONCLUSION: Our results suggest that monoaminergic neuromodulation plays an important role in the physiopathology of HI brain injury that may represent a good therapeutic target.
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