CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
Prog Neurobiol. 2019 Nov;182:101680. doi: 10.1016/j.pneurobio.2019.101680. Epub 2019 Aug 9.
The composition of cerebrospinal and brain interstitial fluids is ensured by barriers between the blood and the brain parenchyma (the blood-brain barrier) and between the blood and the cerebrospinal fluid (the blood-cerebrospinal fluid barrier). Barrier function results from the combination of tight junctions between cells that impair solute flux via the paracellular pathway, cell membrane transporters that enable selective transcellular solute passage, and intracellular metabolizing enzymes that transform molecules in transit. Collectively, they comprise a chemical surveillance system, essential to protect the brain from toxicants, microorganisms, and other harmful compounds. Conversely, this chemical surveillance system compromises the brain delivery of many pharmacologic agents against brain cancer and brain metastasis, neurodegenerative diseases, and brain infections. Despite their importance, the mechanisms underlying the regulation of the components of this chemical surveillance system in response to alterations in the composition of blood and brain fluids are still poorly understood. We propose that odorant receptors, vomeronasal receptors and taste receptors, recently identified at brain barriers might be upstream components of this surveillance system. These chemosensory receptors are strategically placed to monitor the composition of blood, cerebrospinal and brain interstitial fluids. Upon ligand-binding, they may deploy the action of transporters and detoxifying enzymes or other unprecedented functions in brain barrier cells, to cope with alterations in the composition of blood and brain cerebrospinal and interstitial fluids, working as guardians of the central nervous system.
脑脊髓液和脑间质液的组成由血脑实质（血脑屏障）和血液与脑脊液之间的屏障（血脑脊液屏障）之间的屏障来保证。屏障功能源于细胞之间紧密连接的组合，这些连接阻碍溶质通过细胞旁途径的流动，细胞膜转运蛋白使溶质选择性地穿过细胞，以及细胞内代谢酶使运输中的分子发生转化。它们共同构成了一个化学监测系统，对于保护大脑免受毒物、微生物和其他有害化合物的侵害至关重要。然而，这种化学监测系统会影响许多针对脑癌和脑转移、神经退行性疾病和脑部感染的药物在大脑中的传递。尽管它们很重要，但对于化学监测系统的组成部分如何响应血液和脑液成分的变化进行调节的机制仍知之甚少。我们提出，最近在脑屏障中发现的气味受体、犁鼻器受体和味觉受体可能是该监测系统的上游成分。这些化学感觉受体被战略性地放置在可以监测血液、脑脊液和脑间质液组成的位置。在配体结合后，它们可能会在脑屏障细胞中部署转运蛋白和解毒酶或其他以前未知的功能，以应对血液和脑脑脊液和间质液成分的变化，作为中枢神经系统的守护者。
