Neuroprotection assessment by topographic electroencephalographic analysis: effects of a sodium channel blocker to reduce polymorphic delta activity following ischaemic brain injury in rats.
The spatiotemporal electroencephalogram (EEG) pathology associated with brain injury was studied using high-resolution, 10-electrode cortical EEG mapping in a rat model of middle cerebral artery occlusion (MCAo). Using this model we evaluated the ability of the novel sodium channel blocker and neuroprotective agent RS100642 to resolve injury-induced EEG abnormalities as a measure of neurophysiological recovery from brain injury. The middle cerebral artery (MCA) was occluded for 1 h during which a dramatic loss of EEG power was measured over the injured cortex with near complete recovery upon reperfusion of blood to the MCA region in all rats. The resultant progression of the MCAo/reperfusion injury (6-72 h) included the appearance of diffuse polymorphic delta activity (PDA), as visually indicated by the presence of high-amplitude slow-waves recorded from both brain hemispheres. PDA was associated with large increases in EEG power, particularly evident in outer 'peri-infarct' regions of the ipsilateral parietal cortex as visualized using topographic EEG mapping. Post-injury treatment with RS100642 (1.0 mg/kg, i.v.) significantly reduced the PDA activity and attenuated the increase in EEG power throughout the course of the injury. These effects were associated with a reduction in brain infarct volume and improved neurological function. These methods of EEG analysis may be helpful tools to evaluate the physiological recovery of the brain from injury in humans following treatment with an experimental neuroprotective compound.
Williams
Anthony J
AJ
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. spcanthony.williams@na.amedd.army.mil
Lu
Xi-Chun M
XC
Hartings
Jed A
JA
Tortella
Frank C
FC
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D003700:Delta Rhythm / Q000187:drug effects* / Q000379:methods; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D015222:Sodium Channels / Q000502:physiology*
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels