Wellman Steven M, Kozai Takashi D Y
Department of Bioengineering, ‡Center for the Neural Basis of Cognition, §Center for Neuroscience, ∥McGowan Institute of Regenerative Medicine, and ⊥NeuroTech Center, University of Pittsburgh Brain Institute, University of Pittsburgh , Pittsburgh, Pennsylvania 15213, United States.
ACS Chem Neurosci. 2017 Dec 20;8(12):2578-2582. doi: 10.1021/acschemneuro.7b00403. Epub 2017 Nov 9.
Neurochemical sensing probes are a valuable diagnostic and therapeutic tool that can be used to study neurodegenerative diseases involving deficiencies in neurotransmitter signaling. However, implantation of these biosensors can elicit a harmful tissue response that alters the neurochemical environment within the brain. Transmission of chemical messengers via neurons is impeded by a barrier-forming glial scar that occurs within weeks after insertion followed by progressive neurodegeneration, attenuating signal sensitivity. Emerging research reveals that non-neuronal cells also influence the neurochemical milieu following injury both directly and indirectly. The reactivity of both microglia and astrocytes to inserted probes have been extensively studied in the past yet there remains other glial subtypes in the brain, such as oligodendrocytes and their precursors, the myelin structures they form, as well as vascular-bound pericytes, that have the potential to contribute significantly to the inflammation due to their responsibility to maintain tissue homeostasis. A brief overview of how tissue injury alters the neurochemical makeup followed by alternative potential targets of investigation and novel strategies to enhance the chemical sensing abilities of implantable probes will be discussed.
神经化学传感探针是一种有价值的诊断和治疗工具，可用于研究涉及神经递质信号传导缺陷的神经退行性疾病。然而，植入这些生物传感器会引发有害的组织反应，从而改变大脑内的神经化学环境。插入后数周内形成的胶质瘢痕形成屏障，阻碍了化学信使通过神经元的传递，随后是进行性神经退行性变，减弱了信号敏感性。新出现的研究表明，非神经元细胞在损伤后也直接或间接地影响神经化学环境。过去已经广泛研究了小胶质细胞和星形胶质细胞对插入探针的反应性，但大脑中仍存在其他胶质细胞亚型，如少突胶质细胞及其前体、它们形成的髓鞘结构，以及血管周围的周细胞，由于它们负责维持组织稳态，因此有可能对炎症产生重大影响。本文将简要概述组织损伤如何改变神经化学组成，随后讨论其他潜在的研究靶点以及增强可植入探针化学传感能力的新策略。
