Kempuraj Duraisamy, Dourvetakis Kirk D, Cohen Jessica, Valladares Daniel Seth, Joshi Rhitik Samir, Kothuru Sai Puneeth, Anderson Tristin, Chinnappan Baskaran, Cheema Amanpreet K, Klimas Nancy G, Theoharides Theoharis C
Dr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United States.
College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, United States.
Front Cell Neurosci. 2024 Oct 25;18:1491952. doi: 10.3389/fncel.2024.1491952. eCollection 2024.
Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism of disease pathogenesis is not understood, certain biomarkers provide valuable insight into the disease pathogenesis, severity, progression and therapeutic efficacy. These markers can be used to assess pathophysiological status of brain cells including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, and blood-brain barrier (BBB) disruption. Damage or derangements in tight junction (TJ), adherens junction (AdJ), and gap junction (GJ) components of the BBB lead to increased permeability and neuroinflammation in various brain disorders including neurodegenerative disorders. Thus, neuroinflammatory markers can be evaluated in blood, cerebrospinal fluid (CSF), or brain tissues to determine neurological disease severity, progression, and therapeutic responsiveness. Chronic inflammation is common in age-related neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia. Neurotrauma/traumatic brain injury (TBI) also leads to acute and chronic neuroinflammatory responses. The expression of some markers may also be altered many years or even decades before the onset of neurodegenerative disorders. In this review, we discuss markers of neuroinflammation, and neurodegeneration associated with acute and chronic brain disorders, especially those associated with neurovascular pathologies. These biomarkers can be evaluated in CSF, or brain tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), glial fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane protein 119 (TMEM119), aquaporin, endothelin-1, and platelet-derived growth factor receptor beta (PDGFRβ) are some important neuroinflammatory markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding of brain disorders and neurotherapeutics. Integration of these markers in clinical practice could potentially enhance early diagnosis, monitor disease progression, and improve therapeutic outcomes.
通过激活神经胶质细胞引起的神经血管单元（NVU）炎症和神经元损伤在神经退行性疾病中起关键作用。尽管疾病发病的确切机制尚不清楚，但某些生物标志物为疾病发病机制、严重程度、进展和治疗效果提供了有价值的见解。这些标志物可用于评估包括神经元、星形胶质细胞、小胶质细胞、少突胶质细胞、特殊微血管内皮细胞、周细胞、神经血管单元和血脑屏障（BBB）破坏在内的脑细胞的病理生理状态。血脑屏障紧密连接（TJ）、黏附连接（AdJ）和缝隙连接（GJ）成分的损伤或紊乱会导致包括神经退行性疾病在内的各种脑部疾病的通透性增加和神经炎症。因此，可以在血液、脑脊液（CSF）或脑组织中评估神经炎症标志物，以确定神经疾病的严重程度、进展和治疗反应性。慢性炎症在包括阿尔茨海默病（AD）、帕金森病（PD）和痴呆症在内的与年龄相关的神经退行性疾病中很常见。神经创伤/创伤性脑损伤（TBI）也会导致急性和慢性神经炎症反应。在神经退行性疾病发作前许多年甚至几十年，一些标志物的表达也可能发生改变。在本综述中，我们讨论了与急性和慢性脑部疾病相关的神经炎症和神经退行性变的标志物，特别是那些与神经血管病理相关的标志物。这些生物标志物可以在脑脊液或脑组织中进行评估。神经丝轻链（NfL）、泛素C末端水解酶-L1（UCHL1）、胶质纤维酸性蛋白（GFAP）、离子钙结合衔接分子1（Iba-1）、跨膜蛋白119（TMEM119）、水通道蛋白、内皮素-1和血小板衍生生长因子受体β（PDGFRβ）是一些重要的神经炎症标志物。最近的芯片上血脑屏障模型为深入了解脑部疾病和神经治疗提供了有前景的潜力。将这些标志物整合到临床实践中可能会增强早期诊断、监测疾病进展并改善治疗效果。
