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10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 27849

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Dr. Brandon Lucke-Wold

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Department of Neurosurgery, University of Florida, Gainesville, FL, USA
Interests: neurosurgery; neuroscience; subarachnoid hemorrhage; traumatic brain injury
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we aim to publish a Special Issue entitled 10th Anniversary of Biomedicines—Neuroinflammation and neuroprotection. Neuroinflammation has emerged as a key pathway in the initiation and progression of neurodegeneration. Key data from clinical and preclinical studies have investigated the underlying mechanisms and integral interactions with other pathways, such as ER stress, oxidative stress, and mitochondrial dysfunction. What has yet to be elucidated is the timing of these activities and how these pathways interact with each other to cause disease progression. The focus of this Special Issue is to highlight the interplay that takes places between these pathways, with particular interest being placed on the role of neuroinflammation. We would be happy to entertain pre-clinical and clinical investigations as well as carefully targeted reviews.

Dr. Brandon Lucke-Wold
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

neuroinflammation
neurodegeneration
mechanisms
disease progression
ER stress
oxidative stress
mitochondrial dysfunction

Related Special Issue

Biomedicines: 10th Anniversary in Biomedicines (46 articles)

Published Papers (10 papers)

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Research

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30 pages, 3840 KiB

Open AccessArticle

Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease

by Suzanne M. de la Monte, Ming Tong and Andrew J. Hapel

Biomedicines 2023, 11(9), 2394; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11092394 - 27 Aug 2023

Viewed by 1546

Abstract

Neuroinflammation may be a pathogenic mediator and biomarker of neurodegeneration at the boundary between mild cognitive impairment (MCI) and early-stage Alzheimer’s disease (AD). Whether neuroinflammatory processes are endogenous to the central nervous system (CNS) or originate from systemic (peripheral blood) sources could impact strategies for therapeutic intervention. To address this issue, we measured cytokine and chemokine immunoreactivities in simultaneously obtained lumbar puncture cerebrospinal fluid (CSF) and serum samples from 39 patients including 18 with MCI or early AD and 21 normal controls using a 27-plex XMAP bead-based enzyme-linked immunosorbent assay (ELISA). The MCI/AD combined group had significant (p < 0.05 or better) or statistically trend-wise (0.05 ≤ p ≤ 0.10) concordant increases in CSF and serum IL-4, IL-5, IL-9, IL-13, and TNF-α and reductions in GM-CSF, b-FGF, IL-6, IP-10, and MCP-1; CSF-only increases in IFN-y and IL-7 and reductions in VEGF and IL-12p70; serum-only increases in IL-1β, MIP-1α, and eotaxin and reductions in G-CSF, IL-2, IL-8 and IL-15; and discordant CSF–serum responses with reduced CSF and increased serum PDGF-bb, IL-17a, and RANTES. The results demonstrate simultaneously parallel mixed but modestly greater pro-inflammatory compared to anti-inflammatory or neuroprotective responses in CSF and serum. In addition, the findings show evidence that several cytokines and chemokines are selectively altered in MCI/AD CSF, likely corresponding to distinct neuroinflammatory responses unrelated to systemic pathologies. The aggregate results suggest that early management of MCI/AD neuroinflammation should include both anti-inflammatory and pro-neuroprotective strategies to help prevent disease progression. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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17 pages, 3374 KiB

Open AccessArticle

Curcumae radix Reduces Endoplasmic Reticulum Stress in Mice with Chronic Neuroinflammation

by Seong-Lae Jo, Hyun Yang, Hye Won Lee and Eui-Ju Hong

Biomedicines 2023, 11(8), 2107; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11082107 - 26 Jul 2023

Cited by 2 | Viewed by 773

Abstract

Endoplasmic reticulum (ER) stress is a condition in which the ER protein-folding machinery is impaired, leading to the accumulation of improperly folded proteins and triggering an unfolded-protein response. Excessive ER stress causes cell death and contributes to the development of chronic diseases. Interestingly, there is a bidirectional relationship between ER stress and the nuclear factor-kappa B (NF-κB) pathway. Curcumin, a natural polyphenolic compound found in Curcumae radix, exerts its neuroprotective effects by regulating ER stress and inflammation. Therefore, investigating the potential protective and regulatory effects of curcumin on ER stress, inflammation, and neurodegeneration under chronic neuroinflammatory conditions is of great interest. Mice were pretreated with Curcumae radix extract (CRE) for 19 days and then treated with CRE plus lipopolysaccharide for 1 week. We monitored pro-inflammatory cytokine levels in the serum and ER stress-, inflammation-, and neurodegeneration-related markers in the mouse cerebrum and hippocampus using Western blotting and qRT-PCR. CRE reduced Interleukin-1 beta levels in the blood and brain of mice with lipopolysaccharide-induced chronic inflammation. CRE also suppressed the expression of markers related to the ER stress and NF-κB signaling pathways. The expression of neurodegeneration-related markers was reduced in the mouse cerebrum and hippocampus. CRE exerts neuroprotective effects under chronic inflammatory conditions via multifaceted anti-inflammatory and ER stress-pathway regulatory mechanisms. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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0 pages, 2019 KiB

Open AccessArticle

Ameliorative Effects of Isoeugenol and Eugenol against Impaired Nerve Function and Inflammatory and Oxidative Mediators in Diabetic Neuropathic Rats

by Khalid M. Alharthy, Mohamed F. Balaha, Sushma Devi, Ali Altharawi, Hasan S. Yusufoglu, Rana M. Aldossari, Aftab Alam and Viviana di Giacomo

Biomedicines 2023, 11(4), 1203; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11041203 - 18 Apr 2023

Cited by 2 | Viewed by 1416

Abstract

Diabetic polyneuropathy is characterized by structural abnormalities, oxidative stress, and neuroinflammation. The current study aimed to determine the antinociceptive effects of isoeugenol and eugenol and their combinations in neuropathic pain resulting from streptozotocin (STZ)-induced diabetes and neuroinflammation. Female SD rats were categorized into normal control, diabetic control, and treatment groups. On the 28th day and 45th day, behavioral studies (allodynia and hyperalgesia) were performed to analyze the development and protection of diabetic polyneuropathy. The levels of inflammatory and oxidative mediators, such as superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), catalase, reduced glutathione, and thiobarbituric acid reactive substances (TBARS), were estimated. In addition, the level of nerve growth factor (NGF) was estimated at the end of the study in different groups. The anti-NGF treatment decreased its upregulation in the dorsal root ganglion significantly. The results showed that isoeugenol, eugenol, and their combination have therapeutic potential against neuronal and oxidative damage induced by diabetes. In particular, both compounds significantly affected behavioral function in treated rats and showed neuroprotection against diabetic neuropathy, and their combination had synergistic effects. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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16 pages, 1782 KiB

Open AccessArticle

Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery

by Krzysztof Laudanski, Da Liu, Tony Okeke, Mariana Restrepo and Wilson Y. Szeto

Biomedicines 2022, 10(10), 2364; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102364 - 22 Sep 2022

Cited by 1 | Viewed by 1593

Abstract

We hypothesized that the persistent depletion of neuroprotective markers accompanies neuroinflammation and neurodegeneration in patients after cardiac surgery. A total of 158 patients underwent elective heart surgery with their blood collected before surgery (t_baseline) and 24 h (t_24hr), seven days (t_7d), and three months (t_3m) post-surgery. The patients’ serum was measured for markers of neurodegeneration (τau, τaup181–183, amyloid β1-40/β2-42, and S100), atypical neurodegeneration (KLK6 and NRGN), neuro-injury (neurofilament light/heavy, UC-HL, and GFAP), neuroinflammation (YKL-40 and TDP-43), peripheral nerve damage (NCAM-1), neuroprotection (apoE4, BDNF, fetuin, and clusterin), and vascular smoldering inflammation (C-reactive protein, CCL-28 IL-6, and IL-8). The mortality at 28 days, incidence of cerebrovascular accidents (CVA), and functional status were followed for three months. The levels of amyloid β1-40/β1-42 and NF-L were significantly elevated at all time points. The levels of τau, S100, KLK6, NRGN, and NCAM-1 were significantly elevated at 24 h. A cluster analysis demonstrated groupings around amyloids, KLK6, and NCAM-1. YKL-40, but not TDP-43, was significantly elevated across all time points. BDNF, apoE4, fetuin, and clusterin levels were significantly diminished long-term. IL-6 and IL-8 levles returned to baseline at t_3m. The levels of CRP, CCL-28, and Hsp-70 remained elevated. At 3 months, 8.2% of the patients experienced a stroke, with transfusion volume being a significant variable. Cardiac-surgery patients exhibited persistent peripheral and neuronal inflammation, blood vessel remodeling, and the depletion of neuroprotective factors 3 months post-procedure. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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15 pages, 3442 KiB

Open AccessArticle

Autologous Platelet-Rich Growth Factor Reduces M1 Macrophages and Modulates Inflammatory Microenvironments to Promote Sciatic Nerve Regeneration

by Anjali Yadav, Thamil Selvee Ramasamy, Sheng-Che Lin, Szu-Han Chen, Jean Lu, Ya-Hsin Liu, Fu-I Lu, Yuan-Yu Hsueh, Shau-Ping Lin and Chia-Ching Wu

Biomedicines 2022, 10(8), 1991; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10081991 - 17 Aug 2022

Cited by 8 | Viewed by 2421

Abstract

The failure of peripheral nerve regeneration is often associated with the inability to generate a permissive molecular and cellular microenvironment for nerve repair. Autologous therapies, such as platelet-rich plasma (PRP) or its derivative platelet-rich growth factors (PRGF), may improve peripheral nerve regeneration via unknown mechanistic roles and actions in macrophage polarization. In the current study, we hypothesize that excessive and prolonged inflammation might result in the failure of pro-inflammatory M1 macrophage transit to anti-inflammatory M2 macrophages in large nerve defects. PRGF was used in vitro at the time the unpolarized macrophages (M0) macrophages were induced to M1 macrophages to observe if PRGF altered the secretion of cytokines and resulted in a phenotypic change. PRGF was also employed in the nerve conduit of a rat sciatic nerve transection model to identify alterations in macrophages that might influence excessive inflammation and nerve regeneration. PRGF administration reduced the mRNA expression of tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β), and IL-6 in M0 macrophages. Increased CD206 substantiated the shift of pro-inflammatory cytokines to the M2 regenerative macrophage. Administration of PRGF in the nerve conduit after rat sciatic nerve transection promoted nerve regeneration by improving nerve gross morphology and its targeted gastrocnemius muscle mass. The regenerative markers were increased for regrown axons (protein gene product, PGP9.5), Schwann cells (S100β), and myelin basic protein (MBP) after 6 weeks of injury. The decreased expression of TNFα, IL-1β, IL-6, and CD68⁺ M1 macrophages indicated that the inflammatory microenvironments were reduced in the PRGF-treated nerve tissue. The increase in RECA-positive cells suggested the PRGF also promoted angiogenesis during nerve regeneration. Taken together, these results indicate the potential role and clinical implication of autologous PRGF in regulating inflammatory microenvironments via macrophage polarization after nerve transection. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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22 pages, 3710 KiB

Open AccessArticle

Sleep Disturbance Alters Cocaine-Induced Locomotor Activity: Involvement of Striatal Neuroimmune and Dopamine Signaling

by Soheil Kazemi Roodsari, Yan Cheng, Kirstin M. Reed, Laurie L. Wellman, Larry D. Sanford, Woong-Ki Kim and Ming-Lei Guo

Biomedicines 2022, 10(5), 1161; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051161 - 18 May 2022

Cited by 1 | Viewed by 2332

Abstract

Sleep disorders have high comorbidity with drug addiction and function as major risk factors for developing drug addiction. Recent studies have indicated that both sleep disturbance (SD) and abused drugs could activate microglia, and that increased neuroinflammation plays a critical role in the pathogenesis of both diseases. Whether microglia are involved in the contribution of chronic SDs to drug addiction has never been explored. In this study, we employed a mouse model of sleep fragmentation (SF) with cocaine treatment and examined their locomotor activities, as well as neuroinflammation levels and dopamine signaling in the striatum, to assess their interaction. We also included mice with, or without, SF that underwent cocaine withdrawal and challenge. Our results showed that SF significantly blunted cocaine-induced locomotor stimulation while having marginal effects on locomotor activity of mice with saline injections. Meanwhile, SF modulated the effects of cocaine on neuroimmune signaling in the striatum and in ex vivo isolated microglia. We did not observe differences in dopamine signaling in the striatum among treatment groups. In mice exposed to cocaine and later withdrawal, SF reduced locomotor sensitivity and also modulated neuroimmune and dopamine signaling in the striatum. Taken together, our results suggested that SF was capable of blunting cocaine-induced psychoactive effects through modulating neuroimmune and dopamine signaling. We hypothesize that SF could affect neuroimmune and dopamine signaling in the brain reward circuitry, which might mediate the linkage between sleep disorders and drug addiction. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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Review

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20 pages, 2029 KiB

Open AccessEditor’s ChoiceReview

Stem Cell Therapy for Alzheimer’s Disease: A Scoping Review for 2017–2022

by Yunxiao Duan, Linshuoshuo Lyu and Siyan Zhan

Biomedicines 2023, 11(1), 120; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010120 - 03 Jan 2023

Cited by 3 | Viewed by 5325

Abstract

Alzheimer’s disease (AD) has been a major causal factor for mortality among elders around the world. The treatments for AD, however, are still in the stage of development. Stem cell therapy, compared to drug therapies and many other therapeutic options, has many advantages and is very promising in the future. There are four major types of stem cells used in AD therapy: neural stem cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. All of them have applications in the treatments, either at the (1) cellular level, in an (2) animal model, or at the (3) clinical level. In general, many more types of stem cells were studied on the cellular level and animal model, than the clinical level. We suggest for future studies to increase research on various types of stem cells and include cross-disciplinary research with other diseases. In the future, there could also be improvements in the timeliness of research and individualization for stem cell therapies for AD. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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17 pages, 1324 KiB

Open AccessReview

Group I mGluRs in Therapy and Diagnosis of Parkinson’s Disease: Focus on mGluR5 Subtype

by Shofiul Azam, Md. Jakaria, JoonSoo Kim, Jaeyong Ahn, In-Su Kim and Dong-Kug Choi

Biomedicines 2022, 10(4), 864; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040864 - 07 Apr 2022

Cited by 4 | Viewed by 5338

Abstract

Metabotropic glutamate receptors (mGluRs; members of class C G-protein-coupled receptors) have been shown to modulate excitatory neurotransmission, regulate presynaptic extracellular glutamate levels, and modulate postsynaptic ion channels on dendritic spines. mGluRs were found to activate myriad signalling pathways to regulate synapse formation, long-term potentiation, autophagy, apoptosis, necroptosis, and pro-inflammatory cytokines release. A notorious expression pattern of mGluRs has been evident in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and schizophrenia. Among the several mGluRs, mGluR5 is one of the most investigated types of considered prospective therapeutic targets and potential diagnostic tools in neurodegenerative diseases and neuropsychiatric disorders. Recent research showed mGluR5 radioligands could be a potential tool to assess neurodegenerative disease progression and trace respective drugs’ kinetic properties. This article provides insight into the group I mGluRs, specifically mGluR5, in the progression and possible therapy for PD. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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15 pages, 711 KiB

Open AccessEditor’s ChoiceReview

Gastrointestinal Microbiome and Neurologic Injury

by Eric J. Panther, William Dodd, Alec Clark and Brandon Lucke-Wold

Biomedicines 2022, 10(2), 500; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020500 - 21 Feb 2022

Cited by 25 | Viewed by 4245

Abstract

Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual. Microbes release short-chain fatty acids (SCFAs) that regulate G-protein-coupled receptors to mediate hormone release, neurotransmitter release (i.e., serotonin, dopamine, noradrenaline, γ-aminobutyric acid (GABA), acetylcholine, and histamine), and regulate inflammation and mood. Further gaseous factors (i.e., nitric oxide) are important in regulating inflammation and have a response in injury. Neurologic injuries such as ischemic stroke, spinal cord injury, traumatic brain injury, and hemorrhagic cerebrovascular lesions can all lead to gut dysbiosis. Additionally, unfavorable alterations in the composition of the microbiota may be associated with increased risk for these neurologic injuries due to increased proinflammatory molecules and clotting factors. Interventions such as probiotics, fecal microbiota transplantation, and oral SCFAs have been shown to stabilize and improve the composition of the microbiome. However, the effect this has on neurologic injury prevention and recovery has not been studied extensively. The purpose of this review is to elaborate on the complex relationship between the nervous system and the microbiome and to report how neurologic injury modulates the status of the microbiome. Finally, we will propose various interventions that may be beneficial in the recovery from neurologic injury. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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Other

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19 pages, 851 KiB

Open AccessSystematic Review

Glial Contributions to Lafora Disease: A Systematic Review

by Stefania Della Vecchia, Maria Marchese and Filippo Maria Santorelli

Biomedicines 2022, 10(12), 3103; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123103 - 01 Dec 2022

Viewed by 1376

Abstract

Background: Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and molecular alterations, neuroinflammation has emerged as another key histopathological feature of LD. Methods: To investigate the role of astrocytes and microglia in LD, we performed a systematic review according to the PRISMA statement. PubMed, Scopus, and Web-of-Science database searches were performed independently by two reviewers. Results: Thirty-five studies analyzing the relationship of astrocytes and microglia with LD and/or the effects of anti-inflammatory treatments in LD animal models were identified and included in the review. Although LD has long been dominated by a neuronocentric view, a growing body of evidence suggests a role of glial cells in the disease, starting with the finding that these cells accumulate PBs. We discuss the potential meaning of glial PB accumulations, the likely factors activating glial cells, and the possible contribution of glial cells to LD neurodegeneration and epilepsy. Conclusions: Given the evidence for the role of neuroinflammation in LD, future studies should consider glial cells as a potential therapeutic target for modifying/delaying LD progression; however, it should be kept in mind that these cells can potentially assume multiple reactive phenotypes, which could influence the therapeutic response. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines: Neuroinflammation and Neuroprotection)

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