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BackgroundNeuroinflammation is associated with many conditions that lead to dementia, such as cerebrovascular disorders or Alzheimer’s disease. However, the specific role of neuroinflammation in the progression of cognitive deficits remains unclear. To understand the molecular mechanisms underlying these events we used a rodent model of focal cerebral stroke, which causes deficits in hippocampus-dependent cognitive function.MethodsCerebral stroke was induced by middle cerebral artery occlusion (MCAO). Hippocampus-dependent cognitive function was evaluated by a contextual fear conditioning test. The glial neuroinflammatory responses were investigated by immunohistochemical evaluation and diffusion tensor MRI (DTI). We used knockout mice for P2Y1 (P2Y1KO), a glial ADP/ATP receptor that induces the release of proinflammatory cytokines, to examine the links among P2Y1-mediated signaling, the neuroinflammatory response, and cognitive function.ResultsDeclines in cognitive function and glial neuroinflammatory response were observed after MCAO in both rats and mice. Changes in the hippocampal tissue were detected by DTI as the mean diffusivity (MD) value, which corresponded with the cognitive decline at 4 days, 1 week, 3 weeks, and 2 months after MCAO. Interestingly, the P2Y1KO mice with MCAO showed a decline in sensory-motor function, but not in cognition. Furthermore, the P2Y1KO mice showed neither a hippocampal glial neuroinflammatory response (as assessed by immunohistochemistry) nor a change in hippocampal MD value after MCAO. In addition, wild-type mice treated with a P2Y1-specific antagonist immediately after reperfusion did not show cognitive decline.ConclusionOur findings indicate that glial P2Y1 receptors are involved in the hippocampal inflammatory response. The findings from this study may contribute to the development of a therapeutic strategy for brain infarction, targeting the P2Y1 receptor.

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We developed an MRI-compatible, ultra-thin, flexible stimulator array for the rat brain and performed functional MRI (fMRI) acquisition during direct electrical stimulation of the brain. This technique measured brain activity evoked by direct stimulation of the motor and the somatosensory cortex. In order to avoid MR signal loss due to interferences with the main static field and RF field in the MRI system, the stimulator array was made from a non-magnetic gold electrode of 100-nm thickness on a 2-um-thick parylene substrate. By using this stimulator array, MR images without signal loss around conducting electrode pads were acquired, and fMRI acquisition during concurrent electrical stimulation of the cerebral cortex was achieved. Neuronal activity propagated to distant brain areas from the stimulated motor cortex. Positive blood oxygenation level dependent (BOLD) signals were observed with direct stimulation of the motor cortex, while negative BOLD signals were observed with direct stimulation of the somatosensory cortex. Interestingly, the pattern of brain activity evoked by direct stimulation of the somatosensory cortex was different from that evoked by electrical stimulation of the forepaw.

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