Abstract
BackgroundExistent animal models of migraine are not without drawbacks and limitations. The aim of our study was to evaluate imaging photoplethysmography (PPG) as a method of assessing intracranial blood flow in rats and its changes in response to electrical stimulation of dural trigeminal afferents.MethodsExperiments were carried out with 32 anesthetized adult male Wistar rats. Trigeminovascular system (TVS) was activated by means of electrical stimulation of dural afferents through a closed cranial window (CCW). Parameters of meningeal blood flow were monitored using a PPG imaging system under green illumination with synchronous recording of an electrocardiogram (ECG) and systemic arterial blood pressure (ABP). Two indicators related to blood-flow parameters were assessed: intrinsic optical signals (OIS) and the amplitude of pulsatile component (APC) of the PPG waveform. Moreover, we carried out pharmacological validation of these indicators by determining their sensitivity to anti-migraine drugs: valproic acid and sumatriptan. For statistical analysis the non-parametric tests with post-hoc Bonferroni correction was used.ResultsSignificant increase of both APC and OIS was observed due to CCW electrical stimulation. Compared to saline (n = 11), intravenous administration of both the sumatriptan (n = 11) and valproate (n = 10) by using a cumulative infusion regimen (three steps performed 30 min apart) lead to significant inhibitory effect on the APC response to the stimulation. In contrast, intravenous infusion of any substance or saline did not affect the OIS response to the stimulation. It was found that infusion of either sumatriptan or valproate did not affect the response of ABP or heart rate to the stimulation.ConclusionsImaging PPG can be used in an animal migraine model as a method for contactless assessment of intracranial blood flow. We have identified two new markers of TVS activation, one of which (APC) was pharmacologically confirmed to be associated with migraine. Monitoring of changes in APC caused by CCW electrical stimulation (controlling efficiency of stimulation by OIS) can be considered as a new way to assess the peripheral mechanism of action of anti-migraine interventions.
Highlights
Existent animal models of migraine are not without drawbacks and limitations
We have identified two new markers of Trigeminovascular system (TVS) activation, one of which (APC) was pharmacologically confirmed to be associated with migraine
Monitoring of changes in amplitude of pulsatile component (APC) caused by closed cranial window (CCW) electrical stimulation can be considered as a new way to assess the peripheral mechanism of action of anti-migraine interventions
Summary
Existent animal models of migraine are not without drawbacks and limitations. The aim of our study was to evaluate imaging photoplethysmography (PPG) as a method of assessing intracranial blood flow in rats and its changes in response to electrical stimulation of dural trigeminal afferents. Migraine is a form of primary headache associated with autonomic and sensory disturbances [1]. This disabling disease significantly reduces the quality of life, aggravates the course of comorbid pathologies and is a risk factor for the development of cardiovascular accidents [2,3,4]. It is clear that the search for new treatments requires a preclinical phase During this phase, experiments based on animal migraine models, which allow to transfer the experiment data to clinical practice with a certain degree of confidence, are rather productive [15,16,17]
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