Cortical spreading depression (CSD) is an intense depolarization of neuronal and glial membranes accompanied by a massive disruption of ionic gradients and loss of membrane resistance. It has been shown to be a common therapeutic target for currently prescribed migraine prophylactic drugs and thus is proposed as a useful model for testing novel prophylactic drugs. Creative Biolabs conducts contract studies in the CSD models (KCl-induced & electrical stimulation-induced) for efficacy assessment of new antimigraine drugs.
Introduction of CSD Model of Migraine Aura
Cortical spreading depression (CSD), which is known as a shift in cortical steady potential, results in an increase in the extracellular ions (K+), intracellular ions (Na+ and Ca2+), and neurotransmitter (glutamate). These ionic shifts produce slow direct current (DC) potential shifts that can be recorded extracellularly. Moreover, CSD is associated with changes in cortical parenchymal blood flow. Studies have reported that CSD models are useful tools for testing current and novel prophylactic drugs, providing knowledge on mechanisms of action relevant for migraine. Experimental findings to date suggest that chronic daily administration of certain migraine prophylactic drugs (topiramate, valproate, propranolol, amitriptyline, and methysergide) dose-dependently suppress CSD.
For model induction, animals are anesthetized and placed on a stereotaxic frame. The dura on the left side is exposed and is kept moist with the help of modified synthetic interstitial fluid. Single waves of CSD can be induced using mechanical, electrical, or chemical stimulation of the visual cortex. Chemical stimulation is achieved by the application of high concentration of KCl solution. Electrical stimulation (cathodal pulses) is given by using a concentric bipolar electrode. Currently, electrical stimulation and/or brief applications of high K+ are considered to be the most appropriate CSD-inducing stimuli.
Fig.1 Mechanisms and structures involved in the pathogenesis of migraine with aura. (Costa et al. 2013)
Assessments
Creative Biolabs conducts various assessments for efficacy evaluation of novel prophylactic drugs. The extracellular DC potentials caused by ionic shifts and changes in cerebral blood flow (CBF) occurring during CSD can be recorded. The vascular and parenchymal changes occurring with CSD in anesthetized mice and rats can be examined simultaneously by using optical intrinsic signal (OIS) imaging and electrophysiology. Briefly, the assessments provided by Creative Biolabs include:
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Reference
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