An electrochemical adenosine sensor for in vivo applications

描述（由申请人提供）：腺苷是脑中调节脑血流和神经传递的重要调节剂，并且在病理状况如中风期间具有神经保护作用。四种腺苷受体具有一系列的亲和力和作用。可用于结合并激活这些受体的腺苷浓度控制对腺苷的生理反应。因此，需要快速监测腺苷浓度，以了解腺苷的神经调节作用的时间过程。本提案的目的是开发一种用于监测体内腺苷浓度的快速传感器。该传感器将允许了解在生理和病理条件下可用于激活受体的腺苷的实时浓度分布。我们计划通过开发以下目标来实现这些目标：（1）开发碳纤维微电极作为腺苷传感器，（2）开发碳纳米管修饰的腺苷传感器，以及（3）表征体内刺激的腺苷释放。这种传感器将允许腺苷在大脑中的快速调节作用的第一次测量，并导致对神经调节的动力学有更好的理解。 这项研究将导致更好地了解腺苷如何调节神经传递的基本神经生物学。我们开发的传感器可用于研究腺苷如何调节多巴胺的释放，从而为帕金森病提供新的治疗方法。该传感器还可用于研究调节内源性腺苷浓度的药物的作用，这些药物被提议用于创伤性脑损伤、癫痫发作和中风的神经保护治疗。

DESCRIPTION (provided by applicant): Adenosine is an important modulator in the brain that regulates cerebral blood flow and neurotransmission and is neuroprotective during pathological conditions such as stroke. The four adenosine receptors have a range of affinities and effects. The concentration of adenosine available to bind to and activate these receptors controls the physiological response to adenosine. Therefore, rapid monitoring of adenosine concentrations is required to understand the time course of the neuromodulatory effects of adenosine. The objective of this proposal is to develop a rapid sensor for monitoring adenosine concentrations in vivo. This sensor will allow an understanding of the real-time concentration profile of adenosine available to activate receptors under physiological and pathological conditions. We plan to carry out these objectives by developing the following aims: (1) Development of carbon-fiber microelectrodes as sensors for adenosine, (2) Development of carbon nanotube-modified sensors for adenosine, and (3) Characterization of stimulated adenosine release in vivo. This sensor will allow the first measurements of rapid modulatory effects of adenosine in the brain and lead to a greater understanding of the dynamics of neuromodulation. This research will lead to a better understanding of the basic neurobiology of how adenosine modulates neurotransmission. The sensor we develop could be used to study how adenosine modulates dopamine release, leading to new treatments for Parkinson disease. The sensor could also be utilized to study the effects of drugs that regulate endogenous adenosine concentrations, which are proposed neuroprotective treatments for traumatic brain injury, seizures, and stroke.