Protective effects of regulatory T cells on ischemic brain damage

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The organic cation transporters 3 (= OCT3) was identified as an uptake-2 transporter, responsible for clearance of histamine. Because increasing evidence suggests the involvement of histamine in cerebral ischemia, we investigated the effects of targeted disruption of OCT3 on the severity of ischemic brain damage. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery (MCA) of homozygous Oct3-deficient mice and their wild type littermates. Consequently, targeted disruption of OCT3 significantly increased histamine content in the ischemic cortex and significantly reduced the infarct volume after cerebral ischemia. Furthermore, this disruption prevented the reduction of regulatory T cell proportion after cerebral ischemia. Since repeated administration of L-histidine (a precursor of histamine) to wild-type mice also showed the same effects, our observations suggested that OCT3 is the molecule responsible for clearance of ischemia-induced histamine in the brain and targeted disruption of OCT3 ameliorated ischemic brain damage through an increase in regulatory T cells.