The Effects of a Combination of Ion Channel Inhibitors in Female Rats Following Repeated Mild Traumatic Brain Injury
Autor: | Melinda Fitzgerald, Ryu Takechi, Samra Krakonja, Hannah R. Milbourn, Michael Nesbit, Brooke Fehily, Anna M. B. Black, Carole A. Bartlett, Nathanael J. Yates, Yilin Mao |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
neurotrauma medicine.disease_cause lcsh:Chemistry 0302 clinical medicine Brain Injuries Traumatic Medicine oxidative stress lcsh:QH301-705.5 Spectroscopy Lomerizine Voltage-dependent calcium channel biology General Medicine Calcium Channel Blockers 3. Good health Computer Science Applications medicine.anatomical_structure Drug Therapy Combination Female medicine.drug medicine.medical_specialty node of Ranvier Traumatic brain injury Central nervous system ion channel inhibitors AMPA receptor Catalysis Article Inorganic Chemistry Superoxide dismutase 03 medical and health sciences Internal medicine Animals Physical and Theoretical Chemistry Maze Learning Molecular Biology business.industry Organic Chemistry medicine.disease Rats repeated mild traumatic brain injury 030104 developmental biology Endocrinology lcsh:Biology (General) lcsh:QD1-999 Closed head injury biology.protein business 030217 neurology & neurosurgery Oxidative stress |
Zdroj: | International Journal of Molecular Sciences, Vol 19, Iss 11, p 3408 (2018) International Journal of Molecular Sciences Volume 19 Issue 11 |
ISSN: | 1422-0067 |
Popis: | Following mild traumatic brain injury (mTBI), the ionic homeostasis of the central nervous system (CNS) becomes imbalanced. Excess Ca2+ influx into cells triggers molecular cascades, which result in detrimental effects. The authors assessed the effects of a combination of ion channel inhibitors (ICI) following repeated mTBI (rmTBI). Adult female rats were subjected to two rmTBI weight-drop injuries 24 h apart, sham procedures (sham), or no procedures (normal). Lomerizine, which inhibits voltage-gated calcium channels, was administered orally twice daily, whereas YM872 and Brilliant Blue G, inhibiting &alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and P2X7 receptors, respectively, were delivered intraperitoneally every 48 h post-injury. Vehicle treatment controls were included for rmTBI, sham, and normal groups. At 11 days following rmTBI, there was a significant increase in the time taken to cross the 3 cm beam, as a sub-analysis of neurological severity score (NSS) assessments, compared with the normal control (p < 0.05), and a significant decrease in learning-associated improvement in rmTBI in Morris water maze (MWM) trials relative to the sham (p < 0.05). ICI-treated rmTBI animals were not different to sham, normal controls, or rmTBI treated with vehicle in all neurological severity score and Morris water maze assessments (p > 0.05). rmTBI resulted in increases in microglial cell density, antioxidant responses (manganese-dependent superoxide dismutase (MnSOD) immunoreactivity), and alterations to node of Ranvier structure. ICI treatment decreased microglial density, MnSOD immunoreactivity, and abnormalities of the node of Ranvier compared with vehicle controls (p < 0.01). The authors&rsquo findings demonstrate the beneficial effects of the combinatorial ICI treatment on day 11 post-rmTBI, suggesting an attractive therapeutic strategy against the damage induced by excess Ca2+ following rmTBI. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |