Deafferentation in thalamic and pontine areas in severe traumatic brain injury

Laouchedi, Makhlouf; Galanaud, Damien; Delmaire, Christine; Fernández-Vidal, Sara; Messé, Arnaud; Mesmoudi, S.; Boumghar, Fatima Oulebsir; Pélégrini‐Issac, Mélanie; Puybasset, Louis; Benali, Habib; Perlbarg, Vincent

doi:10.1016/j.neurad.2014.03.001

Cited by 15 publications

(6 citation statements)

References 38 publications

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“…Chronic cleaved-caspase-3 increases were associated with neuronal demyelination in specific thalamic regions which are involved in important neurological functions. Disruption of thalamo-cortical connectivity is one of the recognized features of severe TBI [20,21,22,23]. Neuromodulatory interventions relevant to thalamic functions in the thalamus might promote late functional recovery [44].…”

Section: Discussionmentioning

confidence: 99%

“…This may disrupt brain connectivity within days after injury and continue for years [17,18,19]. Anatomical and functional changes in the thalamus and thalamo-cortical circuits may underlie acute and chronic neurological pathologies associated with functions within the thalamo-cortical system [20,21,22,23,24,25,26]. In addition, a significant impairment in cerebral blood flow in the thalamic regions of patients with mild TBI as compared to healthy controls [27].…”

Section: Introductionmentioning

confidence: 99%

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Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats

Glushakov

Glushakova

Korol

et al. 2018

IJMS

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Traumatic brain injury (TBI) is associated with long-term disabilities and devastating chronic neurological complications including problems with cognition, motor function, sensory processing, as well as behavioral deficits and mental health problems such as anxiety, depression, personality change and social unsuitability. Clinical data suggest that disruption of the thalamo-cortical system including anatomical and metabolic changes in the thalamus following TBI might be responsible for some chronic neurological deficits following brain trauma. Detailed mechanisms of these pathological processes are not completely understood. The goal of this study was to evaluate changes in the thalamus following TBI focusing on cleaved-caspase-3, a specific effector of caspase pathway activation and myelin and microvascular pathologies using immuno- and histochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) in adult Sprague-Dawley rats. Significant increases in cleaved-caspase-3 immunoreactivity in the thalamus were observed starting one month and persisting for at least three months following experimental TBI. Further, the study demonstrated an association of cleaved-caspase-3 with the demyelination of neuronal processes and tissue degeneration in the gray matter in the thalamus, as reflected in alterations of myelinated fiber integrity (luxol fast blue) and decreases in myelin basic protein (MBP) immunoreactivity. The immunofluorescent counterstaining of cleaved-caspase-3 with endothelial barrier antigen (EBA), a marker of blood-brain barrier, revealed limited direct and indirect associations of cleaved caspase-3 with blood-brain barrier damage. These results demonstrate for the first time a significant chronic upregulation of cleaved-caspase-3 in selected thalamic regions associated with cortical regions directly affected by CCI injury. Further, our study is also the first to report that significant upregulation of cleaved-caspase-3 in selected ipsilateral thalamic regions is associated with microvascular reorganization reflected in the significant increases in the number of microvessels with blood-brain barrier alterations detected by EBA staining. These findings provide new insights into potential mechanisms of TBI cell death involving chronic activation of caspase-3 associated with disrupted cortico-thalamic and thalamo-cortical connectivity. Moreover, this study offers the initial evidence that this upregulation of activated caspase-3, delayed degeneration of myelinated nerve fibers and microvascular reorganization with impaired blood-brain barrier integrity in the thalamus might represent reciprocal pathological processes affecting neuronal networks and brain function at the chronic stages of TBI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats

Glushakov

Glushakova

Korol

et al. 2018

IJMS

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“…Therefore, the thalamus acts as the brain’s relay center for the transmission of sensory information. While generally there are no overt lesions within the thalamus following TBI, studies investigating severe TBI populations have consistently reported altered structural properties of the thalamus in the chronic stages of injury including localized atrophy (Warner et al, 2010b), reduced FA (Little et al, 2010), and the association of reduced thalamo-cortical fiber density with unfavorable outcome (Laouchedi et al, 2014). Furthermore, a recent PET study demonstrated increased inflammation in thalamus long after severe TBI regardless of the location of the initial focal injury (Ramlackhansingh et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Hyper-connectivity of the thalamus during early stages following mild traumatic brain injury

Sours

George

Zhuo

et al. 2015

Brain Imaging and Behavior

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The thalamo-cortical resting state functional connectivity of 7 sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6±3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self-reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work.

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“…Understanding the origin of the microstructural changes of brain tissues underpinning functional disconnections is also crucial for unravelling the mechanisms of DOC [18]. Conventional MRI techniques may detect and estimate the gross pathological processes leading to coma and other DOC states.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of Non-Gaussian Diffusion Metrics in Chronic Disorders of Consciousness

et al. 2019

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Diagnostic accuracy of different chronic disorders of consciousness (DOC) can be affected by the false negative errors in up to 40% cases. In the present study, we aimed to investigate the feasibility of a non-Gaussian diffusion approach in chronic DOC and to estimate a sensitivity of diffusion kurtosis imaging (DKI) metrics for the differentiation of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) from a healthy brain state. We acquired diffusion MRI data from 18 patients in chronic DOC (11 VS/UWS, 7 MCS) and 14 healthy controls. A quantitative comparison of the diffusion metrics for grey (GM) and white (WM) matter between the controls and patient group showed a significant (p < 0.05) difference in supratentorial WM and GM for all evaluated diffusion metrics, as well as for brainstem, corpus callosum, and thalamus. An intra-subject VS/UWS and MCS group comparison showed only kurtosis metrics and fractional anisotropy differences using tract-based spatial statistics, owing mainly to macrostructural differences on most severely lesioned hemispheres. As a result, we demonstrated an ability of DKI metrics to localise and detect changes in both WM and GM and showed their capability in order to distinguish patients with a different level of consciousness.

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Deafferentation in thalamic and pontine areas in severe traumatic brain injury

Cited by 15 publications

References 38 publications

Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats

Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats

Hyper-connectivity of the thalamus during early stages following mild traumatic brain injury

Feasibility of Non-Gaussian Diffusion Metrics in Chronic Disorders of Consciousness

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