Early cerebrovascular and long-term neurological modifications ensue following juvenile mild traumatic brain injury in male mice
Neurobiology of Disease. 2020-07-01; 141: 104952
DOI: 10.1016/j.nbd.2020.104952
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Ichkova A(1), Rodriguez-Grande B(1), Zub E(2), Saudi A(2), Fournier ML(1), Aussudre J(1), Sicard P(3), Obenaus A(4), Marchi N(5), Badaut J(6).
Author information:
(1)CNRS UMR5287, University of Bordeaux, Bordeaux, France.
(2)Cerebrovascular and Glia Research Laboratory, Department of Neuroscience, Institute of Functional Genomics (UMR 5203 CNRS-U1191 INSERM, University of Montpellier), Montpellier, France.
(3)INSERM, CNRS, Université de Montpellier, PhyMedExp, IPAM, Montpellier, France.
(4)CNRS UMR5287, University of Bordeaux, Bordeaux, France; Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, USA; Basic Science Department, Loma Linda University School of Medicine, Loma Linda, CA, USA; Center for Glial-Neuronal Interactions, Division of Biomedical Sciences, UC Riverside, Riverside, CA, USA; Department of Pediatrics, University of California, Irvine, Irvine, CA, USA.
(5)Cerebrovascular and Glia Research Laboratory, Department of Neuroscience, Institute of Functional Genomics (UMR 5203 CNRS-U1191 INSERM, University of Montpellier), Montpellier, France. Electronic address: .
(6)CNRS UMR5287, University of Bordeaux, Bordeaux, France; Basic Science Department, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address: .
Clinical evidence suggests that a mild traumatic brain injury occurring at a juvenile age (jmTBI) may be sufficient to elicit pathophysiological
modifications. However, clinical reports are not adequately integrated with experimental studies examining brain changes occurring post-jmTBI. We monitored the cerebrovascular modifications and assessed the long-term behavioral and electrographic changes resulting from experimental jmTBI. In vivo photoacoustic imaging demonstrated a decrease of cerebrovascular oxygen saturation levels in the impacted area hours post-jmTBI. Three days post-jmTBI oxygenation returned to pre-jmTBI levels, stabilizing at 7 and 30 days after the injury. At the functional level, cortical arterioles displayed no NMDA vasodilation response, while vasoconstriction induced by thromboxane receptor agonist was enhanced at 1 day post-jmTBI. Arterioles showed abnormal NMDA vasodilation at 3 days post-jmTBI, returning to normality at 7 days post injury. Histology showed
changes in vessel diameters from 1 to 30 days post-jmTBI. Neurological evaluation indicated signs of anxiety-like behavior up to 30 days post-jmTBI. EEG recordings performed at the cortical site of impact 30 days post-jmTBI did not indicate seizures activity, although it revealed a reduction of gamma waves as compared to age matched sham. Histology showed decrease of neuronal filament staining. In conclusion, experimental jmTBI triggers an early cerebrovascular hypo‑oxygenation in vivo and faulty vascular reactivity. The exact topographical coherence and the direct casualty between early cerebrovascular changes and the observed long-term neurological modifications remain to be investigated. A potential translational value for cerebro-vascular oxygen monitoring in jmTBI is discussed.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.