A low-power, wireless, and implantable microstimulator system on chip with smart powering management, immediate neural signal acquisition, and wireless rechargeable system is proposed. A system controller with parity checking handles the adjustable stimulus parameters for the stimulated objective. In the current paper, the rat's intra-cardiac electrogram is employed as the stimulated model in the animal study, and it is sensed by a low-voltage and low-power monitoring analog front end. The power management unit, which includes a rectifier, battery charging and detection, and a regulator, is used for the power control of the internal circuits. The stimulation data and required clock are extracted by a phase-locked-loop-based phase shift keying demodulator from an inductive AC signal. The full chip, which consumes 48 μW only, is fabricated in a TSMC 0.35 μm 2P4M standard CMOS process to perform the monitoring and pacing functions with inductively powered communication in the in vivo study.
Inhibition and deletion of soluble epoxide hydrolase (sEH) has been suggested to ameliorate infarction in experimental ischemic stroke possibly via vasoactive epoxyeicosatrienoic acids. However, it is unknown whether the neuroprotective mechanisms involve alteration of post-ischemic neuronal transmission and neurotrophic signaling. We used a permanent middle cerebral artery occlusion (MCAO) model in adult wild-type mice with the sEH inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA) post-treatment and in sEH knockout (sEH KO) mice. We found that sensorimotor recovery was significantly enhanced after MCAO in both AUDA-treated and sEH KO mice, with decreased sEH activity and brain infarction. Decreased post-ischemic long-term potentiation (iLTP) was observed in an ex vivo hippocampal oxygen-glucose deprivation model. Tropomyosin receptor kinase B (TrkB) activation, rather than glutamate receptor alteration, was consistently found after the different manipulations. Immunohistochemistry further revealed peri-infarct neuronal TrkB activation and microvasculature augmentation in AUDA-treated and sEH KO mice, suggesting parallel neurovascular enhancement. Mechanistically, pretreatment with a selective TrkB antagonist ANA12 countered the effect of iLTP attenuation induced by sEH deletion ex vivo and abolished the infarct reduction in vivo. Together, the neuroprotective effects of sEH inhibition and gene deletion can both be mediated partially via enhancement of TrkB signaling which attenuated post-ischemic neuroexcitation and neurological deficits.
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