Mishra Asht Mangal, Bai Xiaoxiao, Sanganahalli Basavaraju G, Waxman Stephen G, Shatillo Olena, Grohn Olli, Hyder Fahmeed, Pitkänen Asla, Blumenfeld Hal
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Core Center for Quantitative Neuroscience with Magnetic Resonance, Yale University, New Haven, Connecticut, United States of America.
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
PLoS One. 2014 Apr 18;9(4):e95280. doi: 10.1371/journal.pone.0095280. eCollection 2014.
Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.
创伤性脑损伤（TBI）约占后天性癫痫的10%。尽管创伤后癫痫发生的机制尚不清楚，但导致神经元同步性改变的神经网络破坏仍是一种可行的候选机制。我们检验了一个假设，即静息态BOLD-fMRI功能连接可以揭示与损伤皮层相连的脑区的网络异常，并且这些变化与功能损害，特别是癫痫发生有关。在7只成年雄性Sprague-Dawley大鼠中使用侧方流体冲击伤诱导TBI，4个月后在9.4T下进行功能成像。作为对照，我们使用了6只假手术动物，它们接受了所有手术操作但未受伤。进行脑电图（EEG）-功能磁共振成像（fMRI）以测量静息功能连接。在功能成像一周后，给大鼠植入双极颅骨电极。恢复后，大鼠在EEG监测下进行戊四氮（PTZ）惊厥易感性测试。对于图像分析，在每个半球分析四对感兴趣区域：同侧和对侧额叶和顶叶皮层、海马体和丘脑。对功能成像数据应用高通和低通滤波器。计算比较受伤大鼠和假手术大鼠的组统计数据以及各区域之间随时间的相关性。最后，对大鼠进行灌注以进行组织学检查。在功能成像期间，没有一只大鼠出现癫痫样放电。然而，PTZ测试显示受伤大鼠与对照组相比惊厥易感性增加。组统计数据显示，与假手术动物相比，损伤侧同侧和对侧顶叶皮层之间以及顶叶皮层与海马体之间的连接性降低。受伤动物在同侧和对侧顶叶皮层与其他区域之间也存在异常的负连接。我们的数据首次提供了用静息态BOLD-fMRI评估实验性TBI后功能连接异常的证据。
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