The role of serotonin in pathofisiology of hypertonia following antenatal hypoxia-ischemia

• Grant number: 13/01723-6
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: July 16, 2013
• End date: August 15, 2013
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Maria Inês Nogueira
• Grantee: Maria Inês Nogueira
• Visiting researcher: Alexander Drobyshevsky
• Visiting researcher institution: NorthShore University HealthSystem, United States
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

This project aims to join both labs studing the effects of low level of oxygen in the brain near or after birth. Our model of neonatal anoxia in rats and Dr. Sidharta Tan´s model of pre-natal hipoxia-hischemia (H-I) in rabbits. Both, already well established and producing morphofunctional alterations that resembles the affects observed in human cerebral palsy (CP). Preliminary findings and previous studies give support to propose a novel pathophysiological mechanism for the development of motor deficits in CP. It was observed in those anoxia/hipoxia evaluated animals a low level of 5-HT in the brain but a high one in the spinal cord. Therefore, the elevated spinal serotonin level after antenatal H-I injury might be contributing to the muscle hypertonia in newborns rabbit kits. We hypothesize that selective injury to the rostral serotonergic brain stem nuclei projecting to brain, cause depletion of brain serotonin and stimulate the raphe caudal group, projecting to spinal cord, what results in elevated spinal serotonin e hence promotes the muscle hypertonia condition. This hypothesis will be approached by the following steps using immunehistochemistry to 5-HT transmitter, receptor and transporter as well as stereological methods in the biological material prepared in the NorthShore Univ. but sliced, reacted and mounted in Brazil, according to the following steps. 1) establish the number of serotonergic projections, receptor and transported expression in injured brains and spinal cords, 2) determine the level of injury to serotonergic neurons in brain stem nuclei projecting to brain and projecting to spinal cord 3) establish the origin of elevated spinal serotonin content (neuronal or vascular). The collaborative proposal will utilize strength of the unique clinically relevant model of CP expressing pronounced phenotype of sensorimotor injury in newborns, developed and studied in the only lab at the US, in partnership with the substantial expertise in neurotransmitter histopathological characterization of injury in small animals at the Universidade de São Paulo. As expected outcome of the project we aim to establish collaboration between our labs in the area of perinatal brain injury, produce a publication in a high impact journal and obtain preliminary data for a joint grant application. (AU)