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Diffuse traumatic brain injury in mice is associated with a transient mismatch of cerebral blood flow and energy metabolism

Arkan, Sertan LU ; Gottschalk, Michael LU orcid ; Ansar, Saema LU ; Bömers, Jesper Peter ; Ehinger, Johannes LU orcid ; Elmér, Eskil LU orcid ; Chamkha, Imen LU ; Karlsson, Michael LU and Marklund, Niklas LU orcid (2025) In Journal of Cerebral Blood Flow and Metabolism
Abstract

Axonal injuries commonly contribute to poor functional outcomes following traumatic brain injury (TBI). To assess cerebral blood flow (CBF) and energy metabolic disturbances in a TBI model of widespread axonal injury, we exposed 105 adult mice to the central (midline) fluid percussion injury (cFPI) diffuse TBI model, or sham injury, and used 9.4 T magnetic resonance (MR) arterial spin labeling (ASL), cortical and hippocampal mitochondrial respiration, and hippocampal MR spectroscopy at 1- and 7-days post-injury (dpi). Widespread, bilateral CBF reductions were observed at day 1 dpi, changes that were normalized by 7 dpi. However, cortical and hippocampal mitochondrial respiration and reactive oxygen species (ROS) production was not... (More)

Axonal injuries commonly contribute to poor functional outcomes following traumatic brain injury (TBI). To assess cerebral blood flow (CBF) and energy metabolic disturbances in a TBI model of widespread axonal injury, we exposed 105 adult mice to the central (midline) fluid percussion injury (cFPI) diffuse TBI model, or sham injury, and used 9.4 T magnetic resonance (MR) arterial spin labeling (ASL), cortical and hippocampal mitochondrial respiration, and hippocampal MR spectroscopy at 1- and 7-days post-injury (dpi). Widespread, bilateral CBF reductions were observed at day 1 dpi, changes that were normalized by 7 dpi. However, cortical and hippocampal mitochondrial respiration and reactive oxygen species (ROS) production was not significantly altered at 1 and 7 dpi. Moreover, hippocampal volumes, evaluated by MRI, were not altered by cFPI, and by immunohistochemistry only a few apoptotic hippocampal cells were observed. By MRS, evidence of delayed (7 dpi) membrane disruption (phosphocholine and glycerophosphocholine) and glutamate/glutamine increase were observed. While widespread traumatic axonal pathology associated with functional impairments is observed in this TBI model, early CBF alterations were transient and did not translate into significant energy metabolic disturbances. Instead, the delayed hippocampal metabolite changes observed by MRS may contribute to the functional impairment observed in this diffuse TBI model.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
axonal injury, central fluid percussion injury, cerebral blood flow, energy metabolism, mitochondria, Traumatic brain injury (TBI)
in
Journal of Cerebral Blood Flow and Metabolism
publisher
Nature Publishing Group
external identifiers
  • pmid:40801336
  • scopus:105013492685
ISSN
0271-678X
DOI
10.1177/0271678X251364136
language
English
LU publication?
yes
id
4be091fc-9823-4c58-ae70-8141c1ecb19a
date added to LUP
2025-11-20 08:47:38
date last changed
2025-11-21 03:00:10
@article{4be091fc-9823-4c58-ae70-8141c1ecb19a,
  abstract     = {{<p>Axonal injuries commonly contribute to poor functional outcomes following traumatic brain injury (TBI). To assess cerebral blood flow (CBF) and energy metabolic disturbances in a TBI model of widespread axonal injury, we exposed 105 adult mice to the central (midline) fluid percussion injury (cFPI) diffuse TBI model, or sham injury, and used 9.4 T magnetic resonance (MR) arterial spin labeling (ASL), cortical and hippocampal mitochondrial respiration, and hippocampal MR spectroscopy at 1- and 7-days post-injury (dpi). Widespread, bilateral CBF reductions were observed at day 1 dpi, changes that were normalized by 7 dpi. However, cortical and hippocampal mitochondrial respiration and reactive oxygen species (ROS) production was not significantly altered at 1 and 7 dpi. Moreover, hippocampal volumes, evaluated by MRI, were not altered by cFPI, and by immunohistochemistry only a few apoptotic hippocampal cells were observed. By MRS, evidence of delayed (7 dpi) membrane disruption (phosphocholine and glycerophosphocholine) and glutamate/glutamine increase were observed. While widespread traumatic axonal pathology associated with functional impairments is observed in this TBI model, early CBF alterations were transient and did not translate into significant energy metabolic disturbances. Instead, the delayed hippocampal metabolite changes observed by MRS may contribute to the functional impairment observed in this diffuse TBI model.</p>}},
  author       = {{Arkan, Sertan and Gottschalk, Michael and Ansar, Saema and Bömers, Jesper Peter and Ehinger, Johannes and Elmér, Eskil and Chamkha, Imen and Karlsson, Michael and Marklund, Niklas}},
  issn         = {{0271-678X}},
  keywords     = {{axonal injury; central fluid percussion injury; cerebral blood flow; energy metabolism; mitochondria; Traumatic brain injury (TBI)}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Journal of Cerebral Blood Flow and Metabolism}},
  title        = {{Diffuse traumatic brain injury in mice is associated with a transient mismatch of cerebral blood flow and energy metabolism}},
  url          = {{http://dx.doi.org/10.1177/0271678X251364136}},
  doi          = {{10.1177/0271678X251364136}},
  year         = {{2025}},
}