Olfactory Bulb Pinprick Induction of Cortical Spreading Depolarizations

Cortical spreading depolarization (CSD) is a wave of cellular depolarization followed by prolonged depression of neuronal activity and is associated with a broad array of neurological diseases, including migraine with aura, traumatic brain injury, and stroke. Traditional CSD induction methods for animal studies have included pinprick, concentrated potassium chloride (KCl) application, and electrical stimulation. These methods are invasive and can cause injury to the cortex. Recently, a non-invasive approach using optogenetics has become available, but requires the use of transgenic mice or transfection of an optogene, which limits its wide adoption. Here, we describe a novel approach using olfactory bulb needle insertion in rodents to induce CSD. We also included KCl-induced CSDs as a comparator in the same mice. Olfactory bulb pinprick resulted in CSDs on every attempt (n = 18/18) as confirmed with optical intrinsic signal imaging. Histological analysis revealed that needle disruption in the caudal olfactory bulb, which is continuous with the cerebral cortex, may account for the propagation of CSD from the olfactory bulb to the cortex. Olfactory bulb pinprick reliably induces CSD and is non-invasive with respect to cortex. The approach may prove to be useful in rodent studies where maintenance of cortical integrity is important.