Alteration of the cortical spreading depolarization in the mouse defective in translocator protein 18 kDa.

Cortical spreading depolarization (CSD) has been implicated in neurological disorders, such as migraine, traumatic brain injury, and stroke. Since neurovascular and inflammatory responses of the cerebral cortex associated with CSD play a critical role in the exaggeration and expansion of the lesions, understanding the molecular mechanisms underlying these phenomena would be indispensable for the development of therapeutic interventions for disorders with CSD. Given that the mitochondrial protein, translocator protein 18 kDa (TSPO), plays a role in cellular metabolism and inflammation, we hypothesized that TSPO can modulate the susceptibility of the brain to CSD. To address this issue, we examined the physiological and molecular changes in cortical tissue under the influence of evoked CSD in TSPO-knockout mice. Histological analysis corroborated that TSPO-knockout mice developed six-layered structures with neuronal and glial cells comparable with those in wild-type mice. In vivo electrophysiology under anesthesia showed that mice with TSPO deletion reduced the number of CSD generation compared with the control group. This change in the CSD was associated with impaired induction of inflammatory genes such as IL-1β, Cox2, and Ccl2. Interestingly, TSPO gene deletion had a protective effect on CSD-induced disruption of the blood-brain barrier function with less extravasation of the Evans blue administered systemically. Collectively, these results highlighted a novel role of TSPO in neurovascular and inflammatory responses as sequelae of CSD.