Voltage-dependent Na+/K+ ion channel blockade fails to ameliorate behavioral deficits after traumatic brain injury in the rat.
Traumatic brain injury (TBI) induces massive, transient ion flux, after impact. This may be via agonist gated channels, such as the muscarinic, cholinergic or NMDA receptor, or via voltage-dependent channels. Pharmacological blockade of the former, is neuroprotective in most TBI models, but the role of voltage-dependent Na+/K+ channels has not been tested. We have therefore tested the hypothesis that intraventricular tetrodotoxin (TTX) (20 microliters, 5 mM) induced blockade of post-TBI ion flux will prevent cytotoxic cell swelling, Na+ and K+ flux, and behavioral deficit. Microdialysis demonstrated blockade of [K+]d flux in the TTX group compared to controls. Behavioral evaluation of motor (days 1-5) and memory function (days 11-15) after TBI revealed no beneficial effect in the TTX group compared to controls. Thus, although evidence of reduced ionic flux was demonstrated in the TTX group, memory and behavior were unaffected, suggesting that agonist-operated channel-mediated ion flux is more important after TBI.
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0631, USA.
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Lyeth
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Hamm
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Bullock
D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology / Q000523:psychology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004594:Electrophysiology; D007276:Injections, Intraventricular; D015640:Ion Channel Gating / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015221:Potassium Channels; D015222:Sodium Channels; D013779:Tetrodotoxin