Investigating subcortical effects of cortical spreading depression in rats

Migraine is seen approximately in 20% of the population and is one of the debilitating disorders in adults leading to economic loss due to headache and other associated symptoms. Cortical spreading depression (CSD) is an intrinsic brain phenomenon that plays an important role in migraine pathogenesis and considered to initiate migraine attacks. The effect of CSD on subcortical structures and on behaviour remain unclear. There are very few studies investigating direct subcortical spread or indirect effects of CSD in animals and those studies were performed under general anesthesia. In this study, effects of CSD is investigated by recording electrocorticogram (ECoG) in subcortical structures such as cauda-putamen, amigdala and thalamus. In addition, mobilization, immobility, eating, drinking, turning, grooming behaviour is analyzed through automated behaviour recording device (Laboras). Simultaneously, ultrasonic pain calls and chirp sounds by rats are investigated via laboratory animal sound recording device.In this study, CSD caused behavior alterations such as pain related freezing and immobility. CSD induced freezing and immobility were blocked with valproic acid. Brain c-fos activation pattern was investigated in brain and subcortical structures and it was shown that valproic acid significantly blocked c-fos activation in brain stem and nociceptive pain related trigeminal nucleus caudalis (TNC), amygdala and thalamic reticular nucleus (TRN). This is an important study for the discovery of acute efficacy of valproic acid in migraine and role of TRN for this effect.