| Abstract No.: | C-A3014 |
| Country: | Canada |
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| Title: | DEFORMATION BASED MORPHOLOGICAL ANALYSIS OF 3D ANATOMICAL MRI IMAGES TO CHARACTERIZE THE REGIONAL CHANGES IN BRAIN VOLUME IN NEONATAL RATS EXPOSED TO PAIN |
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| Authors/Affiliations: | Hasan Jason Cakiroglu1, Claire-Dominique Walker3,4,5, Celeste Johnston 2,5,6, Barry J. Bedell1
1McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal QC, Canada
2Alan Edwards Centre for Research on Pain, McGill University, Montreal QC, Canada
3Department of Psychiatry, McGill University, Montreal QC, Canada
4Dept of Anatomy & Cell Biology, McGill University, Montreal QC, Canada
5Neuroscience Division, Douglas Hospital Research Center, Montreal QC, Canada
6 School of Nursing, McGill University, Montreal QC, Canada
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| Content: | Studies on early neonatal experiences have shown that the longer an infant remains in the neonatal intensive care unit, the more painful procedures they will experience, which results in altered neuro-development. These studies have focused on the behavioural and physiological changes over time, leading to inferences about the relationship between pain and changes in regional brain volume, and have implicated such regions as the cerebral cortex, limbic system, thalamus, and hypothalamus. Animal models of repeated early pain are useful to understand underlying mechanisms, however, there are currently no studies which have directly and non-invasively quantified these potential regional brain structural changes in neonatal rats subjected to formalin pain in the first 2 weeks of life over time.
Objective: The aim of this study is to use deformation based morphometry of 3D anatomical MRI images to examine the differences in brain structures between infant rat pups with early exposure to untreated repeated formalin-induced acute pain compared to control, saline-injected rats.
Materials and Methods: Anatomical MRI data was collected from both control (2 saline injections/day between post-natal days [PND]3-14, n=7) and treatment (2 formalin injections/day between PND3-14, n=7) rats on PND14, 36 and 70 respectively. MRI images were registered to a single representative scan to produce a population-specific average model at each time point. Statistics were computed on the deformation fields in Matlab to assess the regional changes within the brain.
Results: Our preliminary data revealed that the formalin treated group at PND14 compared to controls had significant (p < 0.05, corrected for multiple comparisons) hypertrophy in the basomedial amygdala and caudate putamen, which receive afferents from the anterior cingulate cortex and secondary sensory areas of the neocortex in addition to several thalamic nuclei that are implicated in pain pathways. Formalin treated rats at PND70 also had significant hypertrophy in the basomedial amygdala, as well as in medial parabrachial nucleus and medial forbrain bundle. In addition, regional atrophy of the olfactory bulb was observed in formalin treated animals at PND14, as well as in the medial entorhinal cortex and primary sensosomatory cortex in formalin treated animals at PND70.
Conclusions: Our results suggest thats exposure to acute repeated pain in neonatal rats results in extensive structural brain reorganization as early as PND14. The increased basomedial amygdalar volume is consistent with the possibility of hyperactivity and dendritic sprouting demonstrated in this area under chronic stress conditions. At PND70, we observed more extensive regional atrophy in the formalin group compared to controls, suggestive of a negative and long-term impact of early pain on this region.
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