The Imbalance of Astrocytic Mitochondrial Dynamics Following Blast-Induced Traumatic Brain Injury
| dc.contributor.author | Guilhaume-Correa, Fernanda | en |
| dc.contributor.author | Pickrell, Alicia M. | en |
| dc.contributor.author | VandeVord, Pamela J. | en |
| dc.date.accessioned | 2023-02-10T14:43:27Z | en |
| dc.date.available | 2023-02-10T14:43:27Z | en |
| dc.date.issued | 2023-01-24 | en |
| dc.date.updated | 2023-02-10T14:28:27Z | en |
| dc.description.abstract | Mild blast-induced traumatic brain injury (bTBI) is a modality of injury that has been of major concern considering a large number of military personnel exposed to explosive blast waves. bTBI results from the propagation of high-pressure static blast forces and their subsequent energy transmission within brain tissue. Exposure to this overpressure energy causes a diffuse injury that leads to acute cell damage and, if chronic, leads to detrimental long-term cognitive deficits. The literature presents a neuro-centric approach to the role of mitochondria dynamics dysfunction in bTBI, and changes in astrocyte-specific mitochondrial dynamics have not been characterized. The balance between fission and fusion events is known as mitochondrial dynamics. As a result of fission and fusion, the mitochondrial structure is constantly altering its shape to respond to physiological stimuli or stress, which in turn affects mitochondrial function. Astrocytic mitochondria are recognized to play an essential role in overall brain metabolism, synaptic transmission, and neuron protection. Mitochondria are vulnerable to injury insults, leading to the increase in mitochondrial fission, a mechanism controlled by the GTPase dynamin-related protein (Drp1) and the phosphorylation of Drp1 at serine 616 (p-Drp1<sup>s616</sup>). This site is critical to mediate the Drp1 translocation to mitochondria to promote fission events and consequently leads to fragmentation. An increase in mitochondrial fragmentation could have negative consequences, such as promoting an excessive generation of reactive oxygen species or triggering cytochrome c release. The aim of the present study was to characterize the unique pattern of astrocytic mitochondrial dynamics by exploring the role of DRP1 with a combination of in vitro and in vivo bTBI models. Differential remodeling of the astrocytic mitochondrial network was observed, corresponding with increases in p-Drp1<sup>S616</sup> four hours and seven days post-injury. Further, results showed a time-dependent reactive astrocyte phenotype transition in the rat hippocampus. This discovery can lead to innovative therapeutics targets to help prevent the secondary injury cascade after blast injury that involves mitochondria dysfunction. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Guilhaume-Correa, F.; Pickrell, A.M.; VandeVord, P.J. The Imbalance of Astrocytic Mitochondrial Dynamics Following Blast-Induced Traumatic Brain Injury. Biomedicines 2023, 11, 329. | en |
| dc.identifier.doi | https://doi.org/10.3390/biomedicines11020329 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/113774 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | blast-induced traumatic brain injury | en |
| dc.subject | mild | en |
| dc.subject | acute | en |
| dc.subject | sub-acute | en |
| dc.subject | astrocytes | en |
| dc.subject | mitochondrial dynamics | en |
| dc.subject | fission and dynamin-related protein | en |
| dc.title | The Imbalance of Astrocytic Mitochondrial Dynamics Following Blast-Induced Traumatic Brain Injury | en |
| dc.title.serial | Biomedicines | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |