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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 53719

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Special Issue Editors

Dr. Mootaz Salman

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Guest Editor

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
Interests: neuroscience; aquaporins; blood-brain barrier (BBB); neurodegeneration; organ-on-a-chip; glia; astrocytes; trumatic brain injuries (TBI); stroke; stem cells; spinal cord injuries; glymphatic system

Dr. Philip Kitchen

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Guest Editor

School of Life and Health Sciences, Aston University, Birmingham, UK
Interests: aquaporins; membrane transport; water homeostasis; blood-brain barrier (BBB); edema

Prof. Dr. Roslyn Bill

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Guest Editor

College of Health & Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
Interests: membrane proteins; recombinant protein production in yeast; aquaporins; water homeostasis; cytotoxic oedema

Special Issue Information

Dear colleagues,

CNS injuries including stroke, traumatic brain injury (TBI), and spinal cord injury are among the most common causes of disability and death worldwide.

There is a clear and unmet clinical need to identify new drug targets, biomarkers, and therapeutics for CNS injuries. Understanding the injury and molecular mechanisms of injury, recovery, and neuroprotection is important to launch new effective therapies; however, despite ground-breaking developments in basic and fundamental research, there is a severe lack of effective therapeutics for the treatment of CNS injuries and prevention of long-term consequences.

In this Special Issue, we welcome the submission of research articles, short reports, case studies, and traditional reviews. The issue is a forum for scientific communications, evidence-based discussion, opinions, and perspectives on the latest advancements in the science of CNS injuries. We particularly encourage the submission of reports on molecular mechanisms, genetics, proteomics, metabolomics and biomarkers, studies of therapeutic interventions and re-purposing of drugs, CNS drug delivery, studies that address the use and limitations of current preclinical animal models, and recent advances concerning in vitro and organ-on-a-chip models. We will also consider submissions regarding early and late medical complications in CNS injuries (brain and spinal cord edema, impaired energy metabolism, neurodegeneration, neuroinflammation, deep vein thrombosis, pulmonary embolism, infections, etc.)

This Special Issue will summarize what has already been achieved and the discoveries, approaches, and technical developments that can open up the doors to better care for CNS injuries.

Dr. Mootaz Salman
Dr. Philip Kitchen
Prof. Dr. Roslyn M. Bill
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

Stroke
TBI
Brain edema
SCI
Spinal cord edema
Neuroinflammation
Neurodegeneration

Published Papers (13 papers)

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Research

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12 pages, 1001 KiB

Open AccessArticle

Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs

by Kinga Borowicz-Reutt and Monika Banach

Int. J. Mol. Sci. 2022, 23(19), 11328; https://doi.org/10.3390/ijms231911328 - 26 Sep 2022

Cited by 3 | Viewed by 1686

Abstract

Trimetazidine (TMZ), an anti-ischemic drug for improving cellular metabolism, is mostly administered to patients with poorly controlled ischemic heart disease (IHD). Since IHD is considered the most frequent causative factor of cardiac arrhythmias, and these often coexist with seizure disorders, we decided to investigate the effect of TMZ in the electroconvulsive threshold test (ECT) and its influence on the action of four first-generation antiepileptic drugs in the maximal electroshock test (MES) in mice. The TMZ (up to 120 mg/kg) did not affect the ECT, but applied at doses of 20–120 mg/kg it decreased the antielectroshock action of phenobarbital. The TMZ (50–120 mg/kg) reduced the effect of phenytoin, and, when administered at a dose of 120 mg/kg, it diminished the action of carbamazepine. All of these revealed interactions seem to be pharmacodynamic, since the TMZ did not affect the brain levels of antiepileptic drugs. Furthermore, the combination of TMZ with valproate (but not with other antiepileptic drugs) significantly impaired motor coordination, evaluated using the chimney test. Long-term memory, assessed with a passive-avoidance task, was not affected by either the TMZ or its combinations with antiepileptic drugs. The obtained results suggest that TMZ may not be beneficial as an add-on therapy in patients with IHD and epilepsy. Full article

(This article belongs to the Special Issue CNS Injuries)

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16 pages, 2101 KiB

Open AccessArticle

Inflammatory Response and Secondary White Matter Damage to the Corpus Callosum after Focal Striatal Stroke in Rats

by Rafael Rodrigues Lima, Ana Carolina Alves Oliveira, Rafael Monteiro Fernandes, Priscila Cunha Nascimento, Marco Aurelio M. Freire and Walace Gomes-Leal

Int. J. Mol. Sci. 2022, 23(6), 3179; https://doi.org/10.3390/ijms23063179 - 16 Mar 2022

Cited by 4 | Viewed by 2165

Abstract

Stroke is one of the leading causes of death and long-term disabilities worldwide, resulting in a debilitating condition occasioned by disturbances in the cerebral vasculature. Primary damage due to metabolic collapse is a quick outcome following stroke, but a multitude of secondary events, including excitotoxicity, inflammatory response, and oxidative stress cause further cell death and functional impairment. In the present work, we investigated whether a primary ischemic damage into the dorsal striatum may cause secondary damage in the circumjacent corpus callosum (CC). Animals were injected with endothelin-1 and perfused at 3, 7, 14, and 30 post-lesion days (PLD). Sections were stained with Cresyl violet for basic histopathology and immunolabeled by antibodies against astrocytes (anti-GFAP), macrophages/microglia (anti-IBA1/anti MHC-II), oligodendrocytes (anti-TAU) and myelin (anti-MBP), and Anti-Nogo. There were conspicuous microgliosis and astrocytosis in the CC, followed by later oligodendrocyte death and myelin impairment. Our results suggest that secondary white matter damage in the CC follows a primary focal striatal ischemia in adult rats. Full article

(This article belongs to the Special Issue CNS Injuries)

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17 pages, 4376 KiB

Open AccessArticle

Induced Neurodifferentiation of hBM-MSCs through Activation of the ERK/CREB Pathway via Pulsed Electromagnetic Fields and Physical Stimulation Promotes Neurogenesis in Cerebral Ischemic Models

by Hee-Jung Park, Ju-Hye Choi, Myeong-Hyun Nam and Young-Kwon Seo

Int. J. Mol. Sci. 2022, 23(3), 1177; https://doi.org/10.3390/ijms23031177 - 21 Jan 2022

Cited by 4 | Viewed by 2367

Abstract

Stroke is among the leading causes of death worldwide, and stroke patients are more likely to live with permanent disabilities even after treatment. Several treatments are being developed to improve the quality of life of patients; however, these treatments still have important limitations. Our study thus sought to evaluate the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) at various pulsed electromagnetic field (PEMF) frequencies. Furthermore, the effects of selected frequencies in vivo were also evaluated using a mouse ischemia stroke model. Cell proliferation decreased by 20% in the PEMF group, as demonstrated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, and lactate dehydrogenase (LDH) secretion increased by approximately 10% in an LDH release assay. Fluorescence-activated cell sorting (FACS) analysis demonstrated that CD73 and CD105 were downregulated in the PEMF group at 60 Hz. Moreover, microtubule-associated protein 2 (MAP-2) and neurofilament light chain (NF-L) were upregulated in cell cultures at 60 and 75 Hz. To assess the effects of PEMF in vivo, cerebral ischemia mice were exposed to a PEMF at 60 Hz. Neural-related proteins were significantly upregulated in the PEMF groups compared with the control and cell group. Upon conducting rotarod tests, the cell/PEMF group exhibited significant differences in motor coordination at 13 days post-treatment when compared with the control and stem-cell-treated group. Furthermore, the cell and cell/PEMF group exhibited a significant reduction in the expression of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-

α

) and interferon-gamma (IFN-γ) in the induced ischemic area compared with the control. Collectively, our findings demonstrated that PEMFs at 60 and 75 Hz could stimulate hBM-MSCs neural differentiation in vitro, in addition to promoting neurogenesis to enhance the functional recovery process by reducing the post-stroke inflammatory reaction. Full article

(This article belongs to the Special Issue CNS Injuries)

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14 pages, 8912 KiB

Open AccessArticle

Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke

by Shervin Banitalebi, Nadia Skauli, Samuel Geiseler, Ole Petter Ottersen and Mahmood Amiry-Moghaddam

Int. J. Mol. Sci. 2022, 23(3), 1117; https://doi.org/10.3390/ijms23031117 - 20 Jan 2022

Cited by 8 | Viewed by 2442

Abstract

There is an urgent need to better understand the mechanisms involved in scar formation in the brain. It is well known that astrocytes are critically engaged in this process. Here, we analyze incipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically, there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mobility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation. Full article

(This article belongs to the Special Issue CNS Injuries)

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23 pages, 6727 KiB

Open AccessArticle

Long-Term Effects of Neural Precursor Cell Transplantation on Secondary Injury Processes and Functional Recovery after Severe Cervical Contusion-Compression Spinal Cord Injury

by Alexander Younsi, Guoli Zheng, Lennart Riemann, Moritz Scherer, Hao Zhang, Mohamed Tail, Maryam Hatami, Thomas Skutella, Andreas Unterberg and Klaus Zweckberger

Int. J. Mol. Sci. 2021, 22(23), 13106; https://doi.org/10.3390/ijms222313106 - 03 Dec 2021

Cited by 12 | Viewed by 2592

Abstract

Cervical spinal cord injury (SCI) remains a devastating event without adequate treatment options despite decades of research. In this context, the usefulness of common preclinical SCI models has been criticized. We, therefore, aimed to use a clinically relevant animal model of severe cervical SCI to assess the long-term effects of neural precursor cell (NPC) transplantation on secondary injury processes and functional recovery. To this end, we performed a clip contusion-compression injury at the C6 level in 40 female Wistar rats and a sham surgery in 10 female Wistar rats. NPCs, isolated from the subventricular zone of green fluorescent protein (GFP) expressing transgenic rat embryos, were transplanted ten days after the injury. Functional recovery was assessed weekly, and FluoroGold (FG) retrograde fiber-labeling, as well as manganese-enhanced magnetic resonance imaging (MEMRI), were performed prior to the sacrifice of the animals eight weeks after SCI. After cryosectioning of the spinal cords, immunofluorescence staining was conducted. Results were compared between the treatment groups (NPC, Vehicle, Sham) and statistically analyzed (p < 0.05 was considered significant). Despite the severity of the injury, leading to substantial morbidity and mortality during the experiment, long-term survival of the engrafted NPCs with a predominant differentiation into oligodendrocytes could be observed after eight weeks. While myelination of the injured spinal cord was not significantly improved, NPC treated animals showed a significant increase of intact perilesional motor neurons and preserved spinal tracts compared to untreated Vehicle animals. These findings were associated with enhanced preservation of intact spinal cord tissue. However, reactive astrogliosis and inflammation where not significantly reduced by the NPC-treatment. While differences in the Basso–Beattie–Bresnahan (BBB) score and the Gridwalk test remained insignificant, animals in the NPC group performed significantly better in the more objective CatWalk XT gait analysis, suggesting some beneficial effects of the engrafted NPCs on the functional recovery after severe cervical SCI. Full article

(This article belongs to the Special Issue CNS Injuries)

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25 pages, 5851 KiB

Open AccessArticle

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

by Pablo Bonilla, Joaquim Hernandez, Esther Giraldo, Miguel A. González-Pérez, Ana Alastrue-Agudo, Hoda Elkhenany, María J. Vicent, Xavier Navarro, Michael Edel and Victoria Moreno-Manzano

Int. J. Mol. Sci. 2021, 22(11), 5966; https://doi.org/10.3390/ijms22115966 - 31 May 2021

Cited by 22 | Viewed by 5258

Abstract

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments. Full article

(This article belongs to the Special Issue CNS Injuries)

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Review

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14 pages, 1150 KiB

Open AccessReview

Edema after CNS Trauma: A Focus on Spinal Cord Injury

by Mostafa Seblani, Patrick Decherchi and Jean-Michel Brezun

Int. J. Mol. Sci. 2023, 24(8), 7159; https://doi.org/10.3390/ijms24087159 - 12 Apr 2023

Cited by 5 | Viewed by 2268

Abstract

Edema after spinal cord injury (SCI) is one of the first observations after the primary injury and lasts for few days after trauma. It has serious consequences on the affected tissue and can aggravate the initial devastating condition. To date, the mechanisms of the water content increase after SCI are not fully understood. Edema formation results in a combination of interdependent factors related to mechanical damage after the initial trauma progressing, along with the subacute and acute phases of the secondary lesion. These factors include mechanical disruption and subsequent inflammatory permeabilization of the blood spinal cord barrier, increase in the capillary permeability, deregulation in the hydrostatic pressure, electrolyte-imbalanced membranes and water uptake in the cells. Previous research has attempted to characterize edema formation by focusing mainly on brain swelling. The purpose of this review is to summarize the current understanding of the differences in edema formation in the spinal cord and brain, and to highlight the importance of elucidating the specific mechanisms of edema formation after SCI. Additionally, it outlines findings on the spatiotemporal evolution of edema after spinal cord lesion and provides a general overview of prospective treatment strategies by focusing on insights to prevent edema formation after SCI. Full article

(This article belongs to the Special Issue CNS Injuries)

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13 pages, 293 KiB

Open AccessReview

Optogenetics for Understanding and Treating Brain Injury: Advances in the Field and Future Prospects

by Yuwen Sun, Manrui Li, Shuqiang Cao, Yang Xu, Peiyan Wu, Shuting Xu, Qian Pan, Yadong Guo, Yi Ye, Zheng Wang, Hao Dai, Xiaoqi Xie, Xiameng Chen and Weibo Liang

Int. J. Mol. Sci. 2022, 23(3), 1800; https://doi.org/10.3390/ijms23031800 - 04 Feb 2022

Cited by 7 | Viewed by 3365

Abstract

Optogenetics is emerging as an ideal method for controlling cellular activity. It overcomes some notable shortcomings of conventional methods in the elucidation of neural circuits, promotion of neuroregeneration, prevention of cell death and treatment of neurological disorders, although it is not without its own limitations. In this review, we narratively review the latest research on the improvement and existing challenges of optogenetics, with a particular focus on the field of brain injury, aiming at advancing optogenetics in the study of brain injury and collating the issues that remain. Finally, we review the most current examples of research, applying photostimulation in clinical treatment, and we explore the future prospects of these technologies. Full article

(This article belongs to the Special Issue CNS Injuries)

22 pages, 4685 KiB

Open AccessReview

Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness

by Alanah Varricchio, Sunita A. Ramesh and Andrea J. Yool

Int. J. Mol. Sci. 2021, 22(21), 11909; https://doi.org/10.3390/ijms222111909 - 02 Nov 2021

Cited by 8 | Viewed by 3561

Abstract

Comprising more than half of all brain tumors, glioblastoma multiforme (GBM) is a leading cause of brain cancer-related deaths worldwide. A major clinical challenge is presented by the capacity of glioma cells to rapidly infiltrate healthy brain parenchyma, allowing the cancer to escape control by localized surgical resections and radiotherapies, and promoting recurrence in other brain regions. We propose that therapies which target cellular motility pathways could be used to slow tumor dispersal, providing a longer time window for administration of frontline treatments needed to directly eradicate the primary tumors. An array of signal transduction pathways are known to be involved in controlling cellular motility. Aquaporins (AQPs) and voltage-gated ion channels are prime candidates as pharmacological targets to restrain cell migration in glioblastoma. Published work has demonstrated AQPs 1, 4 and 9, as well as voltage-gated potassium, sodium and calcium channels, chloride channels, and acid-sensing ion channels are expressed in GBM and can influence processes of cell volume change, extracellular matrix degradation, cytoskeletal reorganization, lamellipodial and filopodial extension, and turnover of cell-cell adhesions and focal assembly sites. The current gap in knowledge is the identification of optimal combinations of targets, inhibitory agents, and drug delivery systems that will allow effective intervention with minimal side effects in the complex environment of the brain, without disrupting finely tuned activities of neuro-glial networks. Based on published literature, we propose that co-treatments using AQP inhibitors in addition to other therapies could increase effectiveness, overcoming some limitations inherent in current strategies that are focused on single mechanisms. An emerging interest in nanobodies as drug delivery systems could be instrumental for achieving the selective delivery of combinations of agents aimed at multiple key targets, which could enhance success in vivo. Full article

(This article belongs to the Special Issue CNS Injuries)

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62 pages, 26626 KiB

Open AccessReview

Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review

by Ruchira M. Jha, Anupama Rani, Shashvat M. Desai, Sudhanshu Raikwar, Sandra Mihaljevic, Amanda Munoz-Casabella, Patrick M. Kochanek, Joshua Catapano, Ethan Winkler, Giuseppe Citerio, J. Claude Hemphill, W. Taylor Kimberly, Raj Narayan, Juan Sahuquillo, Kevin N. Sheth and J. Marc Simard

Int. J. Mol. Sci. 2021, 22(21), 11899; https://doi.org/10.3390/ijms222111899 - 02 Nov 2021

Cited by 25 | Viewed by 5428

Abstract

Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease—providing an overview of the journey from patch-clamp experiments to phase III trials. Full article

(This article belongs to the Special Issue CNS Injuries)

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23 pages, 3868 KiB

Open AccessReview

Dynamics of Choline-Containing Phospholipids in Traumatic Brain Injury and Associated Comorbidities

by Sana Javaid, Talha Farooq, Zohabia Rehman, Ammara Afzal, Waseem Ashraf, Muhammad Fawad Rasool, Faleh Alqahtani, Sary Alsanea, Fawaz Alasmari, Mohammed Mufadhe Alanazi, Metab Alharbi and Imran Imran

Int. J. Mol. Sci. 2021, 22(21), 11313; https://doi.org/10.3390/ijms222111313 - 20 Oct 2021

Cited by 19 | Viewed by 6954

Abstract

The incidences of traumatic brain injuries (TBIs) are increasing globally because of expanding population and increased dependencies on motorized vehicles and machines. This has resulted in increased socio-economic burden on the healthcare system, as TBIs are often associated with mental and physical morbidities with lifelong dependencies, and have severely limited therapeutic options. There is an emerging need to identify the molecular mechanisms orchestrating these injuries to life-long neurodegenerative disease and a therapeutic strategy to counter them. This review highlights the dynamics and role of choline-containing phospholipids during TBIs and how they can be used to evaluate the severity of injuries and later targeted to mitigate neuro-degradation, based on clinical and preclinical studies. Choline-based phospholipids are involved in maintaining the structural integrity of the neuronal/glial cell membranes and are simultaneously the essential component of various biochemical pathways, such as cholinergic neuronal transmission in the brain. Choline or its metabolite levels increase during acute and chronic phases of TBI because of excitotoxicity, ischemia and oxidative stress; this can serve as useful biomarker to predict the severity and prognosis of TBIs. Moreover, the effect of choline-replenishing agents as a post-TBI management strategy has been reviewed in clinical and preclinical studies. Overall, this review determines the theranostic potential of choline phospholipids and provides new insights in the management of TBI. Full article

(This article belongs to the Special Issue CNS Injuries)

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14 pages, 2375 KiB

Open AccessReview

Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances

by Mauro Palmieri, Alessandro Frati, Antonio Santoro, Paola Frati, Vittorio Fineschi and Alessandro Pesce

Int. J. Mol. Sci. 2021, 22(19), 10865; https://doi.org/10.3390/ijms221910865 - 08 Oct 2021

Cited by 17 | Viewed by 3899

Abstract

Traumatic brain injury (TBI) is a condition burdened by an extremely high rate of morbidity and mortality and can result in an overall disability rate as high as 50% in affected individuals. Therefore, the importance of identifying clinical prognostic factors for diffuse axonal injury (DAI) in (TBI) is commonly recognized as critical. The aim of the present review paper is to evaluate the most recent contributions from the relevant literature in order to understand how each single prognostic factor determinates the severity of the clinical syndrome associated with DAI. The main clinical factors with an important impact on prognosis in case of DAI are glycemia, early GCS, the peripheral oxygen saturation, blood pressure, and time to recover consciousness. In addition, the severity of the lesion, classified on the ground of the cerebral anatomical structures involved after the trauma, has a strong correlation with survival after DAI. In conclusion, modern findings concerning the role of reactive oxygen species (ROS) and oxidative stress in DAI suggest that biomarkers such as GFAP, pNF-H, NF-L, microtubule associated protein tau, Aβ42, S-100β, NSE, AQP4, Drp-1, and NCX represent a possible critical target for future pharmaceutical treatments to prevent the damages caused by DAI. Full article

(This article belongs to the Special Issue CNS Injuries)

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22 pages, 1176 KiB

Open AccessReview

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

by Mootaz M. Salman, Zaid Al-Obaidi, Philip Kitchen, Andrea Loreto, Roslyn M. Bill and Richard Wade-Martins

Int. J. Mol. Sci. 2021, 22(9), 4688; https://doi.org/10.3390/ijms22094688 - 28 Apr 2021

Cited by 75 | Viewed by 9539

Abstract

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools. Full article

(This article belongs to the Special Issue CNS Injuries)

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