How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury.
axon
edema
glucose
inflammation
timeline
Journal
Journal of neurotrauma
ISSN: 1557-9042
Titre abrégé: J Neurotrauma
Pays: United States
ID NLM: 8811626
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
pubmed:
11
1
2019
medline:
27
10
2020
entrez:
11
1
2019
Statut:
ppublish
Résumé
Traumatic brain injury (TBI) triggers multiple pathobiological responses with differing onsets, magnitudes, and durations. Identifying the therapeutic window of individual pathologies is critical for successful pharmacological treatment. Dozens of experimental pharmacotherapies have been successfully tested in rodent models, yet all of them (to date) have failed in clinical trials. The differing time scales of rodent and human biological and pathological processes may have contributed to these failures. We compared rodent versus human time scales of TBI-induced changes in cerebral glucose metabolism, inflammatory processes, axonal integrity, and water homeostasis based on published data. We found that the trajectories of these pathologies run on different timescales in the two species, and it appears that there is no universal "conversion rate" between rodent and human pathophysiological processes. For example, the inflammatory process appears to have an abbreviated time scale in rodents versus humans relative to cerebral glucose metabolism or axonal pathologies. Limitations toward determining conversion rates for various pathobiological processes include the use of differing outcome measures in experimental and clinical TBI studies and the rarity of longitudinal studies. In order to better translate time and close the translational gap, we suggest 1) using clinically relevant outcome measures, primarily
Identifiants
pubmed: 30628544
doi: 10.1089/neu.2018.6261
pmc: PMC7643768
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1724-1737Subventions
Organisme : Medical Research Council
ID : G0802251
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : U54 NS100064
Pays : United States
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