Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders

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, prog...

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Main Authors: Duraisamy Kempuraj, Kirk D. Dourvetakis, Jessica Cohen, Daniel Seth Valladares, Rhitik Samir Joshi, Sai Puneeth Kothuru, Tristin Anderson, Baskaran Chinnappan, Amanpreet K. Cheema, Nancy G. Klimas, Theoharis C. Theoharides
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-10-01
Series:Frontiers in Cellular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2024.1491952/full
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author Duraisamy Kempuraj
Kirk D. Dourvetakis
Jessica Cohen
Daniel Seth Valladares
Rhitik Samir Joshi
Sai Puneeth Kothuru
Sai Puneeth Kothuru
Tristin Anderson
Baskaran Chinnappan
Amanpreet K. Cheema
Nancy G. Klimas
Nancy G. Klimas
Theoharis C. Theoharides
Theoharis C. Theoharides
author_facet Duraisamy Kempuraj
Kirk D. Dourvetakis
Jessica Cohen
Daniel Seth Valladares
Rhitik Samir Joshi
Sai Puneeth Kothuru
Sai Puneeth Kothuru
Tristin Anderson
Baskaran Chinnappan
Amanpreet K. Cheema
Nancy G. Klimas
Nancy G. Klimas
Theoharis C. Theoharides
Theoharis C. Theoharides
author_sort Duraisamy Kempuraj
collection DOAJ
description 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.
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spelling doaj-art-a73ca4dfab9d479796e9f282d71810ad2025-08-20T02:11:11ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022024-10-011810.3389/fncel.2024.14919521491952Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disordersDuraisamy Kempuraj0Kirk D. Dourvetakis1Jessica Cohen2Daniel Seth Valladares3Rhitik Samir Joshi4Sai Puneeth Kothuru5Sai Puneeth Kothuru6Tristin Anderson7Baskaran Chinnappan8Amanpreet K. Cheema9Nancy G. Klimas10Nancy G. Klimas11Theoharis C. Theoharides12Theoharis C. Theoharides13Dr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesCollege of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesMiami VA Geriatric Research Education and Clinical Center (GRECC), Miami Veterans Affairs Healthcare System, Miami, FL, United StatesDr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, United StatesDepartment of Immunology, Tufts, University School of Medicine, Boston, MA, United StatesNeurovascular 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.https://www.frontiersin.org/articles/10.3389/fncel.2024.1491952/fullblood-brain barrier disruptionglial cellsneuroinflammatory biomarkersneurodegenerative disordersneurofilament lightneurovascular unit
spellingShingle Duraisamy Kempuraj
Kirk D. Dourvetakis
Jessica Cohen
Daniel Seth Valladares
Rhitik Samir Joshi
Sai Puneeth Kothuru
Sai Puneeth Kothuru
Tristin Anderson
Baskaran Chinnappan
Amanpreet K. Cheema
Nancy G. Klimas
Nancy G. Klimas
Theoharis C. Theoharides
Theoharis C. Theoharides
Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
Frontiers in Cellular Neuroscience
blood-brain barrier disruption
glial cells
neuroinflammatory biomarkers
neurodegenerative disorders
neurofilament light
neurovascular unit
title Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
title_full Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
title_fullStr Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
title_full_unstemmed Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
title_short Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
title_sort neurovascular unit neuroinflammation and neurodegeneration markers in brain disorders
topic blood-brain barrier disruption
glial cells
neuroinflammatory biomarkers
neurodegenerative disorders
neurofilament light
neurovascular unit
url https://www.frontiersin.org/articles/10.3389/fncel.2024.1491952/full
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