Application of mild hypothermia successfully mitigates neural injury in a 3D in-vitro model of traumatic brain injury.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
11
2019
accepted:
07
02
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
14
7
2020
Statut:
epublish
Résumé
Therapeutic hypothermia (TH) is an attractive target for mild traumatic brain injury (mTBI) treatment, yet significant gaps in our mechanistic understanding of TH, especially at the cellular level, remain and need to be addressed for significant forward progress to be made. Using a recently-established 3D in-vitro neural hydrogel model for mTBI we investigated the efficacy of TH after compressive impact injury and established critical treatment parameters including target cooling temperature, and time windows for application and maintenance of TH. Across four temperatures evaluated (31.5, 33, 35, and 37°C), 33°C was found to be most neuroprotective after 24 and 48 hours post-injury. Assessment of TH administration onset time and duration showed that TH should be administered within 4 hours post-injury and be maintained for at least 6 hours for achieving maximum viability. Cellular imaging showed TH reduced the percentage of cells positive for caspases 3/7 and increased the expression of calpastatin, an endogenous neuroprotectant. These findings provide significant new insight into the biological parameter space that renders TH effective in mitigating the deleterious effects of cellular mTBI and provides a quantitative foundation for the future development of animal and preclinical treatment protocols.
Identifiants
pubmed: 32236105
doi: 10.1371/journal.pone.0229520
pii: PONE-D-19-30947
pmc: PMC7112206
doi:
Substances chimiques
Neuroprotective Agents
0
Casp3 protein, rat
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Caspase 7
EC 3.4.22.-
Casp7 protein, rat
EC 3.4.22.60
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0229520Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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