Activation-flow coupling is a fundamental aspect of brain physiology and forms the basis of most functional neuroimaging techniques, yet the mechanisms and mediators of activation-flow coupling remain poorly understood. An improved understanding of these mechanisms and mediators is critical for interpreting functional activation studies in pathological conditions such as Alzheimer's disease, Parkinson's disease, stroke, and schizophrenia. Further, abnormalities in activation-flow coupling may reflect disease-specific pathophysiology and may contribute to differential diagnosis of central nervous system disorders. A rat model system will be developed to characterize activation-flow coupling in the somatosensory cortex in response to electrical forepaw stimulation. Laser Doppler (LD) recordings will be used to characterize changes in velocity, volume, and calculated rCBF in alpha-chloralose anesthetized rats in response to parametric variations in frequency, amplitude, and duration of stimulus. LD has the advantage of being able to monitor changes in rCBF with high temporal resolution and minimal invasiveness. An increase in the signal to noise ratio and reproducibility of LD measurements will be enhanced by using the novel approach of digital signal averaging of recorded responses. The effects of pharmacological manipulation on activation-flow coupling will also be examined. Pharmacological agents that will be administered include the adenosine antagonist-theophylline; a neuronal nitric oxide synthase inhibitor- 7-NINA; a neuronal and endothelial nitric oxide synthase inhibitor - L-NAME; and a NMDA antagonist- MK-801. It is hoped that the establishment of this rat model system and the application of different agents to this system will provide clues as to whether activation-flow coupling is mediated both by neurogenic and metabolic factors.
| Ances, Beau M (2002) New concerns about thalidomide. Obstet Gynecol 99:125-8 |
