Parameters influencing augmentation of cerebral blood flow by cervical spinal cord stimulation

Abstract

Cervical spinal cord stimulation (SCS) has been shown to augment cerebral blood flow (CBF) and protect the brain from focal ischemia. However, the application of SCS in the treatment of cerebral ischemia requires a better understanding of the limits of the cerebrovascular effect and the optimal stimulation parameters. In the present study, we investigated the effects of various stimulation parameters on CBF augmentation, as well as the issue of tachyphylaxis of the CBF response. SCS was performed in adult Sprague Dawley rats, and CBF was assessed using cortical laser Doppler flowmetry (LDF). In separate experimental series, stimulation amplitude, frequency, and pulse width were varied, and the effect on the LDF response was recorded. Finally, using the stimulation parameters found to elicit the strongest LDF response, we examined the effect of lengthening the period of SCS. SCS elicited a robust increase in cortical LDF values as previously demonstrated. The magnitude of the response varied in a dose-dependent fashion with the stimulation amplitude. LDF values increased by more than 80% over baseline with an amplitude of 1.5 mA. The optimal pulse width and frequency of the stimulation were 0.25 ms and 50 Hz, respectively. Lengthening the stimulation period up to 20 minutes resulted in a persistent increase in cerebral LDF values during the entire stimulation period, although the magnitude of this effect diminished to approximately 50% over the baseline after 10 minutes. SCS elicits a robust augmentation in CBF, which lasts the entire stimulation duration. Stimulation parameters required for optimal cerebrovascular response are within normally used therapeutic ranges in the clinical settings. These results provide further evidence that SCS may provide a novel therapeutic strategy for the treatment of cerebral ischemia.