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Reviews in the Neurosciences Dec 2023In recent decade microglia have been found to have a central role in the development of chronic neuropathic pain after injury to the peripheral nervous system. It is... (Review)
Review
In recent decade microglia have been found to have a central role in the development of chronic neuropathic pain after injury to the peripheral nervous system. It is widely accepted that peripheral nerve injury triggers microglial activation in the spinal cord, which contributes to heightened pain sensation and eventually chronic pain states. The contribution of microglia to chronic pain arising after injury to the central nervous system, such as spinal cord injury (SCI), has been less studied, but there is evidence supporting microglial contribution to central neuropathic pain. In this systematic review, we focused on post-SCI microglial activation and how it is linked to emergence and maintenance of chronic neuropathic pain arising after SCI. We found that the number of studies using animal SCI models addressing microglial activity is still small, compared with the ones using peripheral nerve injury models. We have collected 20 studies for full inclusion in this review. Many mechanisms and cellular interactions are yet to be fully understood, although several studies report an increase of density and activity of microglia in the spinal cord, both in the vicinity of the injury and in the spared spinal tissue, as well as in the brain. Changes in microglial activity come with several molecular changes, including expression of receptors and activation of signalling pathways. As with peripheral neuropathic pain, microglia seem to be important players and might become a therapeutic target in the future.
Topics: Animals; Humans; Microglia; Peripheral Nerve Injuries; Chronic Pain; Neuralgia; Spinal Cord Injuries
PubMed: 37490300
DOI: 10.1515/revneuro-2023-0031 -
Neural Regeneration Research Jan 2024Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases, and although most studies focus on its effects on neuronal... (Review)
Review
Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases, and although most studies focus on its effects on neuronal cells, the contribution of non-neuronal cells to the improvement triggered by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested. To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases, Web of Science and PubMed were searched for the effects of high-frequency-repetitive transcranial magnetic stimulation, low-frequency-repetitive transcranial magnetic stimulation, intermittent theta-burst stimulation, continuous theta-burst stimulation, or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells. A total of 52 studies were included. The protocol more frequently used was high-frequency-repetitive magnetic stimulation, and in models of disease, most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and microglial reactivity, a decrease in the release of pro-inflammatory cytokines, and an increase of oligodendrocyte proliferation. The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation. Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol, and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines, reporting the absence of effects on these parameters. In what concerns the use of magnetic stimulation in unlesioned animals or cells, most articles on all four types of stimulation reported a lack of effects. It is also important to point out that the studies were developed mostly in male rodents, not evaluating possible differential effects of repetitive transcranial magnetic stimulation between sexes. This systematic review supports that through modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models. However, it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects, emphasizing the need for more studies in this field.
PubMed: 37488852
DOI: 10.4103/1673-5374.374140 -
Ageing Research Reviews Aug 2023The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence.
METHODS
PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies.
RESULTS
In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥ 4 years (SMD =1.21 [0.37;2.06], p = 0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p < 0.001). Qualitative analysis supported that LCN2 was increased in the brain tissue of AD-related areas, especially in astrocytes and microglia; while LCN2 increased in infarct-related brain areas and over-expressed in astrocytes and macrophages in mixed dementia (MD).
CONCLUSION
The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.
Topics: Humans; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Dementia, Vascular; Lipocalin-2; Mixed Dementias
PubMed: 37330019
DOI: 10.1016/j.arr.2023.101984 -
Behavioural Brain Research Aug 2023Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research... (Review)
Review
BACKGROUND AND AIM
Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research was performed to develop pharmacological or non-pharmacological approaches to treat or improve AD complications. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. Recent evidence suggested that some of the therapeutic effects of MSCs are mediated by the secreted paracrine factors. These paracrine factors, called MSC- conditioned medium (MSC-CM), may stimulate endogenous repair, promote angio- and artery genesis, and reduce apoptosis through paracrine mechanisms. The current study aims to systematically review the advantages of MSC-CM to the development of research and therapeutic concepts for AD management.
MATERIAL AND METHODS
The present systematic review was performed using PubMed, Web of Science, and Scopus from April 2020 to May 2022 following the "Preferred Reporting Items for Systematic Reviews" (PRISMA) guidelines. The keywords, including "Conditioned medium OR Conditioned media OR Stem cell therapy" AND "Alzheimer's," was searched, and finally, 13 papers were extracted.
RESULTS
The obtained data revealed that MSC-CMs might positively affect neurodegenerative diseases prognosis, especially AD, through various mechanisms, including a decrease in neuro-inflammation, reduction of oxidative stress and Aβ formation, modulation of Microglia function and count, reduction of apoptosis, induction of synaptogenesis and neurogenesis. Also, the results showed that MSC-CM administration could significantly improve cognitive and memory function, increase the expression of neurotrophic factors, decrease the production of pro-inflammatory cytokines, improve mitochondrial function, reduce cytotoxicity, and increase neurotransmitter levels.
CONCLUSION
While inhibiting the induction of neuroinflammation could be considered the first therapeutic effect of CMs, the prevention of apoptosis could be regarded as the most crucial effect of CMs on AD improvement.
Topics: Humans; Alzheimer Disease; Culture Media, Conditioned; Neurodegenerative Diseases; Stem Cells; Mesenchymal Stem Cells
PubMed: 37311523
DOI: 10.1016/j.bbr.2023.114543