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Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics.

ABSTRACT: Optogenetics, which uses visible light to control the cells genetically modified with light-gated ion channels, is a powerful tool for precise deconstruction of neural circuitry with neuron-subtype specificity. However, due to limited tissue penetration of visible light, invasive craniotomy and intracranial implantation of tethered optical fibers are usually required for in vivo optogenetic modulation. Here we report mechanoluminescent nanoparticles that can act as local light sources in the brain when triggered by brain-penetrant focused ultrasound (FUS) through intact scalp and skull. Mechanoluminescent nanoparticles can be delivered into the blood circulation via i.v. injection, recharged by 400-nm photoexcitation light in superficial blood vessels during circulation, and turned on by FUS to emit 470-nm light repetitively in the intact brain for optogenetic stimulation. Unlike the conventional "outside-in" approaches of optogenetics with fiber implantation, our method provides an "inside-out" approach to deliver nanoscopic light emitters via the intrinsic circulatory system and switch them on and off at any time and location of interest in the brain without extravasation through a minimally invasive ultrasound interface.

SUBMITTER: Wu X

PROVIDER: S-EPMC6936518 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics.

Wu Xiang X Zhu Xingjun X Chong Paul P Liu Junlang J Andre Louis N LN Ong Kyrstyn S KS Brinson Kenneth K Mahdi Ali I AI Li Jiachen J Fenno Lief E LE Wang Huiliang H Hong Guosong G

Proceedings of the National Academy of Sciences of the United States of America 20191206 52

Optogenetics, which uses visible light to control the cells genetically modified with light-gated ion channels, is a powerful tool for precise deconstruction of neural circuitry with neuron-subtype specificity. However, due to limited tissue penetration of visible light, invasive craniotomy and intracranial implantation of tethered optical fibers are usually required for in vivo optogenetic modulation. Here we report mechanoluminescent nanoparticles that can act as local light sources in the bra ...[more]

PMID: 31811026

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Project description:ObjectivesMinimally invasive extracorporeal circulation (MiECC) is suggested to have favourable impact on blood loss compared to conventional extracorporeal circulation. We aimed to compare the impact of both systems on coagulation.MethodsRandomized trial comparing endogenous thrombin-generating potential early after elective coronary surgery employing either MiECC group (n = 30) or conventional extracorporeal circulation group (n = 30). Secondary outcomes were in vivo thrombin generation, bleeding end points and haemodilution, as well as morbidity and mortality up to 30-day follow-up.ResultsCompared to the conventional extracorporeal circulation group, the MiECC group showed (i) a trend towards a higher early postoperative endogenous thrombin-generating potential (P = 0.06), (ii) lower intraoperative levels of thrombin-antithrombin complex and prothrombin fragment 1 + 2 (P < 0.001), (iii) less haemodilution early postoperatively as measured by haematocrit and weight gain, but without correlation to coagulation factors or bleeding end points. Moreover, half as many patients required postoperative blood transfusion in the MiECC group (17% vs 37%, P = 0.14), although postoperative blood loss did not differ between groups (P = 0.84). Thrombin-antithrombin complex levels (rs = 0.36, P = 0.005) and prothrombin fragment 1 + 2 (rs = 0.45, P < 0.001), but not early postoperative endogenous thrombin-generating potential (rs = 0.05, P = 0.72), showed significant correlation to increased transfusion requirements. The MiECC group demonstrated significantly lower levels of creatine kinase-MB, lactate dehydrogenase and free haemoglobin indicating superior myocardial protection, less tissue damage and less haemolysis, respectively. Perioperative morbidity and 30-day mortality did not differ between groups.ConclusionsConventional but not MiECC is associated with significant intraoperative thrombin generation despite full heparinization. No correlation between coagulation factors or bleeding end points with the degree of haemodilution could be ascertained.Clinicaltrials.gov identifierNCT03216720.

Dataset Information

Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics.

Publications

Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics.

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