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Published July 1, 2017 | Published
Journal Article Open

Craniotomy Alone Results in Defalul Mode Network Dysfunction in the Inmature Rat

Abstract

It remains controversial whether rodents with a craniotomy-only are required, or even appropriate to serve as a sham group to control for the effect of surgery after experimental TBI. Published data show significant molecular and behavioral changes that occur due to craniotomy compared to naïve controls, indicating that craniotomy alone likely constitutes a brain insult. We hypothesized that these confounding effects of craniotomy are also accompanied with alterations in neural circuit dysfunction. We tested this by acquiring resting state functional-MRI data from male, 23 day-old Sprague Dawley rat pups at day 4 post-craniotomy (3mm diameter, -3mm, +4mm left-lateral; intact dura) as well as from age-matched, naïve controls with no craniotomy but with time-matched exposure to isoflurane anesthesia (n= 5/group). Imaging data were acquired on a 7 T Bruker spectrometer using a single-shot, gradient-echo sequence, echo/repetition time: 20/1000ms, 300 repetitions, 128 x 128 matrix, 30 x 30mm field-of-view and 1mm slice-thickness). After typical preprocessing of the time-series data, voxel-wise functional connectivity analysis was then performed by calculating Pearson correlation coefficients between all brain voxels. The Root Mean Square of the correlation values for each voxel were calculated as an index of global functional connectivity (fc), clusterized for the presence of 30 voxels ore more. Large scale, significant (p< 0.01) differences in fc were found between the two groups following group ANOVA. Center of mass for the peaks of the clusters that survived statistical correction for multi voxel comparison were located predominantly in regions previously assigned to the rodent default mode network: bilaterally in auditory, temporal association, and primary visual cortex, and in right retrosplenial cortex and hippocampus. These network alterations provide additional evidence to support the idea that craniotomy-alone constitutes a brain injury, and that it might not always serve as an appropriate control.

Additional Information

© 2017 Mary Ann Liebert. Funding: R01NS27544, R01NS091222, UCLA Easton Labs for Brain Injury, UCLA Steve Tisch BrainSPORT program, UCLA BIRC.

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August 19, 2023
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