Remote Ischemic Post-Conditioning Therapy is Protective in Mouse Model of Traumatic Optic Neuropathy.


Journal

Neuromolecular medicine
ISSN: 1559-1174
Titre abrégé: Neuromolecular Med
Pays: United States
ID NLM: 101135365

Informations de publication

Date de publication:
09 2021
Historique:
received: 26 09 2020
accepted: 30 10 2020
pubmed: 14 11 2020
medline: 17 3 2022
entrez: 13 11 2020
Statut: ppublish

Résumé

Traumatic optic neuropathy (TON) is characterized by visual dysfunction after indirect or direct injury to the optic nerve following blunt head trauma. TON is associated with increased oxidative stress and inflammation resulting in retinal ganglion cell (RGC) death. Remote ischemic post-conditioning (RIC) has been shown to enhance endogenous protective mechanisms in diverse disease models including stroke, vascular cognitive impairment (VCI), retinal injury and optic nerve injury. However, the protective mechanisms underlying the improvement of retinal function and RGC survival after RIC treatment remain unclear. Here, we hypothesized that RIC therapy may be protective following TON by preventing RGC death, oxidative insult and inflammation in the mouse retina. To carry out the study, mice were divided in three different groups (Control, TON and TON + RIC). We harvested retinal tissue 5 days after TON induction for western blotting and histochemical analysis. We observed increased TON-induced retinal cell death compared with controls by cleaved caspase-3 immunohistochemistry. Furthermore, the TON cohort demonstrated increased TUNEL positive cells which were significantly attenuated by RIC. Immunofluorescence data showed that oxidative stress markers dihydroethidium (DHE), NOX-2 and nitrotyrosine expression were elevated in the TON group relative to controls and RIC therapy significantly reduced the expression level of these markers. Next, we found that the proinflammatory cytokine TNF-α was increased and anti-inflammatory IL-10 was decreased in plasma of TON animals, and RIC therapy reversed this expression level. Interestingly, western blotting of retinal tissue showed that RGC marker Brn3a and tight junction proteins (ZO-1 and Occludin), and AMPKα1 expression were downregulated in the TON group compared to controls. However, RIC significantly increased the expression levels of these proteins. Together these data suggest that RIC therapy activates endogenous protective mechanisms which may attenuate TON-induced oxidative stress and inflammation, and improves BRB integrity.

Identifiants

pubmed: 33185833
doi: 10.1007/s12017-020-08631-1
pii: 10.1007/s12017-020-08631-1
doi:

Substances chimiques

Eye Proteins 0
IL10 protein, mouse 0
Pou4f1 protein, mouse 0
Transcription Factor Brn-3A 0
Tumor Necrosis Factor-alpha 0
Superoxides 11062-77-4
Interleukin-10 130068-27-8
3-nitrotyrosine 3604-79-3
Tyrosine 42HK56048U
Cybb protein, mouse EC 1.6.3.-
NADPH Oxidase 2 EC 1.6.3.-
Adenylate Kinase EC 2.7.4.3
Casp3 protein, mouse EC 3.4.22.-
Caspase 3 EC 3.4.22.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

371-382

Informations de copyright

© 2020. Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Muhammad Nadeem (M)

Department of Neurobiology, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA.

Adam Kindelin (A)

Department of Neurosurgery, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA.

Laura Mahady (L)

Department of Neurobiology, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA.

Kanchan Bhatia (K)

Department of Neurosurgery, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA.
School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, 85004, USA.

Md Nasrul Hoda (MN)

Department of Neurobiology, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA.

Andrew F Ducruet (AF)

Department of Neurosurgery, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA.

Saif Ahmad (S)

Department of Neurobiology, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA. saif.ahmad@barrowneuro.org.
Department of Neurosurgery, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85013, USA. saif.ahmad@barrowneuro.org.

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