ABSTRACT
Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80 and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Following 60 episodes of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression. The cerebral blood perfusion was assessed by laser speckle contrast analysis (LASCA) using a PeriCam PSI system. There was a severe reduction in cerebral blood perfusion immediately after the trauma that did not significantly improve within 24 h. The injured mice began to experience reversible sensorimotor function at 9 days postinjury (dpi), which had completely recovered at 28 dpi. However, cognitive deficits and anxiety-like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain-blood barrier and parenchymal edema were found in all pups subjected to 60 insults. Proinflammatory response and reactive gliosis were upregulated at 3 dpi. Degenerated neurons were found in the cerebral cortex and olfactory tubercles at 30 dpi. This mouse model of repetitive brain injury by rotational head acceleration-deceleration partially mimics the major pathophysiological and behavioral events that occur in children with AHT. The resultant hypoxia/ischemia suggests a potential mechanism underlying the secondary rotational acceleration-deceleration-induced brain injury in developing mice.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: Y.P.Z., L.B.E.S., X.Y., C.B.S., J.C.; Methodology: Y.P.Z., Z.G., C.B.S., J.C.; Software: G.W., Y.P.Z., Z.G., T.C., J.C.; Validation: Y.P.Z., C.B.S., J.C.; Formal analysis: G.W., Y.P.Z., Z.G., F.L., T.C., H.L., J.C.; Investigation: G.W., Y.P.Z., Z.G., F.L., T.C., H.L., J.C.; Resources: X.Y., C.B.S., J.C.; Data curation: Y.P.Z., L.B.E.S., C.B.S., J.C.; Writing - original draft: G.W., Y.P.Z., J.C.; Writing - review & editing: Y.P.Z., L.B.E.S., T.C., T.M., X.-M.X., X.Y., C.B.S., J.C.; Visualization: G.W., L.B.E.S., T.C., C.B.S., J.C.; Supervision: Y.P.Z., X.Y., C.B.S., J.C.; Project administration: Y.P.Z., C.B.S., J.C.; Funding acquisition: G.W., Z.G., H.L., X.Y., C.B.S., J.C.
Funding
This work was supported by the NeuroCures Foundation (J.C.), by a Kentucky Spinal Cord and Head Injury Research Board Research Grant (J.C. and C.B.S.), and partially by the National Natural Science Foundation of China (81350013, 31572217 to X.Y.; 81400998 to Z.G.; 81300769 to H.L.) and the China Scholarship Council (G.W.).
Supplementary information
Supplementary information available online at http://dmm.biologists.org/lookup/doi/10.1242/dmm.030387.supplemental
- Received April 27, 2017.
- Accepted November 16, 2017.
- © 2018. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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