Next Article in Journal
Computer Navigation and 3D Printing in the Surgical Management of Bone Sarcoma
Next Article in Special Issue
Chronic Intermittent Mild Whole-Body Hypothermia Is Therapeutic in a Mouse Model of ALS
Previous Article in Journal
Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation
Previous Article in Special Issue
Mitochondrial Cyclosporine A-Independent Palmitate/Ca2+-Induced Permeability Transition Pore (PA-mPT Pore) and Its Role in Mitochondrial Function and Protection against Calcium Overload and Glutamate Toxicity
Open AccessArticle

Genetic Approach to Elucidate the Role of Cyclophilin D in Traumatic Brain Injury Pathology

1
Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky, Lexington, KY 40536, USA
2
Department of Neuroscience, University of Kentucky, Lexington, KY 40508, USA
3
Lexington Veterans’ Affairs Healthcare System, Lexington, KY 40502, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Paolo Bernadi and Evgeny V. Pavlov
Cells 2021, 10(2), 199; https://doi.org/10.3390/cells10020199
Received: 30 November 2020 / Revised: 11 January 2021 / Accepted: 15 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue Mitochondrial Permeability Transition)
Cyclophilin D (CypD) has been shown to play a critical role in mitochondrial permeability transition pore (mPTP) opening and the subsequent cell death cascade. Studies consistently demonstrate that mitochondrial dysfunction, including mitochondrial calcium overload and mPTP opening, is essential to the pathobiology of cell death after a traumatic brain injury (TBI). CypD inhibitors, such as cyclosporin A (CsA) or NIM811, administered following TBI, are neuroprotective and quell neurological deficits. However, some pharmacological inhibitors of CypD have multiple biological targets and, as such, do not directly implicate a role for CypD in arbitrating cell death after TBI. Here, we reviewed the current understanding of the role CypD plays in TBI pathobiology. Further, we directly assessed the role of CypD in mediating cell death following TBI by utilizing mice lacking the CypD encoding gene Ppif. Following controlled cortical impact (CCI), the genetic knockout of CypD protected acute mitochondrial bioenergetics at 6 h post-injury and reduced subacute cortical tissue and hippocampal cell loss at 18 d post-injury. The administration of CsA following experimental TBI in Ppif-/- mice improved cortical tissue sparing, highlighting the multiple cellular targets of CsA in the mitigation of TBI pathology. The loss of CypD appeared to desensitize the mitochondrial response to calcium burden induced by TBI; this maintenance of mitochondrial function underlies the observed neuroprotective effect of the CypD knockout. These studies highlight the importance of maintaining mitochondrial homeostasis after injury and validate CypD as a therapeutic target for TBI. Further, these results solidify the beneficial effects of CsA treatment following TBI. View Full-Text
Keywords: controlled cortical impact; mitochondrial bioenergetics; mitochondria; cyclosporin a; NIM811; mitochondrial permeability transition; Ppif; neuroprotection controlled cortical impact; mitochondrial bioenergetics; mitochondria; cyclosporin a; NIM811; mitochondrial permeability transition; Ppif; neuroprotection
Show Figures

Figure 1

MDPI and ACS Style

Readnower, R.D.; Hubbard, W.B.; Kalimon, O.J.; Geddes, J.W.; Sullivan, P.G. Genetic Approach to Elucidate the Role of Cyclophilin D in Traumatic Brain Injury Pathology. Cells 2021, 10, 199. https://doi.org/10.3390/cells10020199

AMA Style

Readnower RD, Hubbard WB, Kalimon OJ, Geddes JW, Sullivan PG. Genetic Approach to Elucidate the Role of Cyclophilin D in Traumatic Brain Injury Pathology. Cells. 2021; 10(2):199. https://doi.org/10.3390/cells10020199

Chicago/Turabian Style

Readnower, Ryan D.; Hubbard, William B.; Kalimon, Olivia J.; Geddes, James W.; Sullivan, Patrick G. 2021. "Genetic Approach to Elucidate the Role of Cyclophilin D in Traumatic Brain Injury Pathology" Cells 10, no. 2: 199. https://doi.org/10.3390/cells10020199

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop