Delayed treatment of secondary degeneration following acute optic nerve transection using a combination of ion channel inhibitors
| Autor: | Jade E. Kenna, Ryan L. O'Hare Doig, Nathanael J. Yates, Marcus K. Giacci, Wissam Chiha, Carole A. Bartlett, Melinda Fitzgerald, Bethany Eve Ashworth |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty node of Ranvier neurotrauma calcium channel inhibitor secondary degeneration Central nervous system Tau phosphorylation AMPA receptor Pharmacology medicine.disease_cause Neuroprotection lcsh:RC346-429 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience seromas oxidative stress Medicine nerve regeneration lcsh:Neurology. Diseases of the nervous system Ion channel Lomerizine business.industry Calcium channel Antagonist lipid peroxidation optic nerve injury 3. Good health Surgery 030104 developmental biology medicine.anatomical_structure neural regeneration business 030217 neurology & neurosurgery Oxidative stress Research Article medicine.drug |
| Zdroj: | Neural Regeneration Research, Vol 12, Iss 2, Pp 307-316 (2017) Neural Regeneration Research |
| ISSN: | 1673-5374 |
| Popis: | Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca2+ entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO@ pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery. In addition, all of the ion channel inhibitor treated rats were administered with calcium channel antagonist lomerizine hydrochloride. It is important to note that as a result of implantation of the particular pumps required for programmable delivery of therapeutics directly to the injury site, seromas occurred in a significant proportion of animals, indicating infection around the pumps in these animals. Improvements in visual function were observed only when treatment was delayed by 6 hours; phosphorylated Tau was reduced when treatment was delayed by 24 hours or 7 days. Improvements in structure of node/paranode of Ranvier and reductions in oxidative stress indicators were also only observed when treatment was delayed for 6 hours, 24 hours, or 7 days. Benefits of ion channel inhibitors were only observed with time-delayed treatment, suggesting that delayed therapy of Ca2+ ion channel inhibitors produces better neuroprotective effects on secondary degeneration, at least in the presence of seromas. |
| Databáze: | OpenAIRE |
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