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
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