Inhibition of voltage-dependent sodium channels suppresses the functional magnetic resonance imaging response to forepaw somatosensory activation in the rodent.
Results of recent studies suggest that the glutamate-glutamine neurotransmitter cycle between neurons and astrocytes plays a major role in the generation of the functional imaging signal. In the current study, the authors tested the hypothesis that activation of voltage-dependent Na(+) channels is involved in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses during somatosensory activation. The BOLD fMRI and cerebral blood flow (CBF) experiments were performed at 7 Tesla on alpha-chloralose-anesthetized rats undergoing forepaw stimulation before and for successive times after application of lamotrigine, a neuronal voltage-dependent Na+ channel blocker and glutamate release inhibitor. The BOLD fMRI signal changes in response to forepaw stimulation decreased in a time-dependent manner from 6.7% +/- 0.7% before lamotrigine injection to 3.0% +/- 2.5% between 60 and 105 minutes after lamotrigine treatment. After lamotrigine treatment, the fractional increase in CBF during forepaw stimulation was an order of magnitude less than that observed before the treatment. Lamotrigine had no effect on baseline CBF in the somatosensory cortex in the absence of stimulation. These results strongly suggest that activation of voltage-dependent Na+ channels is involved in the BOLD fMRI responses during somatosensory activation of the rat cortex.
Kida
I
I
Department of Diagnostic Radiology, Yale University, New Haven, Connecticut 06510, USA.
Hyder
F
F
Behar
K L
KL
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply; D004558:Electric Stimulation; D005552:Forelimb; D018698:Glutamic Acid / Q000378:metabolism; D007700:Kinetics; D000077213:Lamotrigine; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013003:Somatosensory Cortex / Q000502:physiology*; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology
D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014227:Triazines; D018698:Glutamic Acid; D010100:Oxygen; D000077213:Lamotrigine