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Abnormalities of the dorsal motor nucleus of the vagus in sudden infant death syndrome

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Title: Abnormalities of the dorsal motor nucleus of the vagus in sudden infant death syndrome
Author: Dentremont, Karen
Degree Master of Science - MSc
Program Pathology
Copyright Date: 1998
Abstract: Recent hypotheses concerning the pathogenesis of sudden infant death syndrome (SIDS) have focused on developmental abnormalities of the central nervous system, which are believed to produce cardiorespiratory instability in susceptible infants. The present study was designed to investigate developmental abnormalities in the dorsal motor nucleus of the vagus (DMV) in SIDS. Using serial histological sections of the brainstem from SIDS cases and agematched control cases without neurological disease, morphometric analyzes were performed to compare postnatal changes in 1) the total volume of the DMV, 2) the numerical density of neurons (Nv, cells per mm³), 3) the total number of neurons, and 4) mean neuronal profile area. In the SIDS cases there was a significant increase in the total volume of the DMV (33%), when compared to controls. In SIDS there was a significant decrease in the Nv of neurons (33%), although the total number of neurons did not differ significantly from controls. Mean neuronal profile areas were significantly greater in SIDS for both motor (31&) and non-motor (30%) neurons, when compared to controls. These changes are consistent with an overgrowth of the DMV during early postnatal development. Given the role of the DMV in the autonomic control of breathing and heart rate, this subtle developmental disorder likely contributes to the cardiorespiratory instability characteristic of susceptible infants. Given the possibility that increased expression of insulin-like growth factor I during early postnatal development might contribute to this overgrowth, morphometric analyses were performed on the DMV and hypoglossal nucleus (HN) in transgenic mice, which overexpress IGF-I postnatally, and in normal littermate controls on postnatal day 35. Morphometric variables included 1) the total volumes of the DMV and HN, 2) the Nv of neurons, 3) the total number of neurons, and 4) the mean neuronal profile areas. In transgenic mice there was a significant increase in the volumes of both the DMV (84%) and the HN (30%). The Nv of neurons was significantly reduced in both nuclei in transgenic mice. In the DMV, however, there was a significant increase in the total number of neurons (56%). In the HN, the total number of neurons did not differ significantly between transgenic mice and controls. Mean neuronal profile areas were significantly increased in transgenic mice in both the DMV (35%) and the HN (22%). Available evidence suggests that the increased neuron number in the DMV results from an antiapoptotic effect of IGF-I. In a third experiment, morphometric and stereological analyses were performed in the DMV of rats during normal postnatal development to determine the time course of the progressive and regressive phases of synaptogenesis. The initial phase of synapse proliferation occurred from birth to postnatal day 30, while the regressive phase of synapse elimination occurred after day 30. Recent hypotheses suggest that SIDS results from a failure to eliminate normally extraneous synapses from the brainstem. By knowing the age at which peak synaptic densities occur, one could introduce exogenous growth factors to prevent normal elimination of synapses. Preventing synapse elimination from the brainstem of the rat might be expected to produce an animal model of SIDS. (A scientific formula N[subscript V] used in this abstract could not be reproduced by the software.)
URI: http://hdl.handle.net/2429/8070
Series/Report no. UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/]

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