DigitalUM :: Browsing by Subject "Neuroinflammation"

Browsing by Subject "Neuroinflammation"

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Combined 1-Deoxynojirimycin and Ibuprofen treatment decreases microglial activation, phagocytosis and dopaminergic degeneration in MPTP-treated mice
(Springer , 2020-06-21) Costa, T. C. S.; Fernández Villalba, Emiliano; Izura, V.; Lucas Ochoa, a. M.; Menezes Filho, N. J.; Santana, R.; Olivera, M. de; Araújo, F.; Estrada Esteban, C.; Silva, V.; Costa, S. L.; Herrero Ezquerro, María Trinidad; Medicina Interna; Facultades de la UMU::Facultad de Medicina
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.
Open Access
Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?
(BMC, 2018-11-26) Cuenca Bermejo, Lorena; Sánchez, Consuelo; Estrada Esteban, Cristina; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Gil Martínez, Ana Luisa; Anatomía Humana y Psicobiología
Background: Neuroprotective strategies are becoming relevant to slow down dopaminergic cell death and inflammatory processes related to the progressive neurodegeneration in Parkinson's disease (PD). Interestingly, among others, physical activity (PA) or anti-oxidant agents (such as N-acetyl-L-cysteine, NAC) are common therapeutic strategies. Therefore, this study aims to analyze if there is a synergistic effect of physical activity along with NAC treatment on dopaminergic degeneration and neuroinflammatory response in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism model after subchronic intoxication. Methods: To ascertain this possibility, 48 8-week-old male mice (C57BL/6 strain) were used. Twenty four of them were placed individually in cages where voluntary physical activity was automatically monitored during 30 days and were divided into groups: (i) control; (ii) NAC; (iii) MPTP, and (iv) MPTP+NAC. The other 24 mice were divided into the same four groups but without physical activity. Results: The data collected during the treatment period showed that there was an overall increase in the total running distance in all groups under physical activity, including Parkinsonian animals. However, the monitoring data per day showed that the activity routine by MPTP and MPTP+NAC groups was disrupted by alterations in the circardian rhythm because of MPTP intoxication. Results from post-mortem studies in the substantia nigra pars compacta (SNpc) showed significant decrease in the number of TH+ cells in all MPTP groups. Moreover, TH+ expression in the striatum was significantly decreased in all MPTP groups. Thus, PA + NAC treatment do not protect dopaminergic neurons against a subchronic intoxication of MPTP. Regarding glial response, the results obtained from microglial analysis do not show significant increase in the number of Iba-1+ cell in MPTP+NAC and MPTP+PA + NAC. In the striatum, a significant decrease is observed only in the MPTP+NAC group compared with that of the MPTP group. The microglial results are reinforced by those obtained from the analysis of astroglial response, in which a decrease in the expression of GFAP+ cells are observed in MPTP+NAC and MPTP+PA + NAC compared with MPTP groups both in the SNpc and in the striatum. Finally, from the study of the astroglial response by the co-localization of GFAP/S100b, we described some expression patterns observed based on the severity of the damage produced by the MPTP intoxication in the different treated groups. Conclusions: These results suggest that the combination of physical activity with an anti-oxidant agent does not have a synergistic neuroprotective effect in the nigrostriatal pathway. Our results show a potential positive effect, only due to NAC treatment, on the neuroinflammatory response after subchronic MPTP intoxication. Thus, physical activity is not essential, under these conditions. However, we believe that physical activity, used for therapeutic purposes, has a beneficial long-term effect. In this line, these results open the door to design longer studies to demonstrate its promising effect as neuroprotective strategy.
Open Access
Ferroptosis-relevant mechanisms and biomarkers for therapeutic interventions in traumatic brain injury
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Rui, Tongyu; Li, Qianqian; Song, Shunchen; Gao, Yaxuan; Luo, Chengliang
Traumatic brain injury (TBI) is one of the most significant health care problems worldwide, causing disability and death especially among young individuals. Although a large range of agents and therapies have been proved beneficial to lesions post- TBI to some extent, effective treatments have not been translated to the clinic. As a newly discovered form of iron-dependent regulated cell death, ferroptosis has been implicated in TBI. In this review, we update the current state of knowledge related to second injuries post-TBI, including ferroptosis, oxidative stress, mitochondrial dysfunction, neuroinflammation and so on, which often lead to chronic symptoms and long-term disability. This review systematically summarizes the latest progress in the pathophysiological mechanisms of TBI, with a focus on providing references for proposing new multi- molecular targets for comprehensive therapeutic strategies based on ferroptosis-relevant mechanisms. In addition, biomarkers are essential diagnostic and prognostic tools in TBI. Several biomarkers associated with the outcome of TBI have been listed in this article, such as Pde10a, MDA, UCH-L1, S100A9, S100B, ALDOC, ACSL4, MBP and F2-Isoprostane. Therefore, the understating of ferroptosis-relevant mechanisms and biomarkers may contribute to development of promising therapies for TBI clinical trials.
Open Access
Gentiopicroside alleviates neuroinflammation in Parkinson's disease by mediating microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Shen Hong; Song Hui; Sun Qiang; Biología Celular e Histología
Objective. The study aimed to evaluate the therapeutic potential of gentiopicroside (GPS) in Parkinson's disease (PD) through both in vitro and in vivo experiments, focusing on elucidating the underlying mechanisms of its action. Methods. To achieve this, a PD model was established in C57BL6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by assessment of behavioral changes, pathological alterations, microglial activation, and neuro-inflammation. Simultaneously, a cellular PD model was developed in the BV-2 mouse microglia cell line by exposing them to 1-methyl-4-phenyl-pyridinium (MPP+). The expression of pro-inflammatory molecules was quantified using enzyme-linked immunosorbent assay (ELISA), while pyroptosis was analyzed by flow cytometry with caspase-1/PI double staining. The expression of key factors in the nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway was determined by immunoblotting. Results. The findings revealed that GPS effectively mitigated motor deficits, neurological impairments, microglial activation, and neuroinflammation in the MPTP-induced mouse model of PD. Additionally, GPS protected BV-2 cells from MPP+-induced inflammatory cytokine production and pyroptosis. Mechanistic studies indicated that GPS may exert its neuroprotective effects by inactivating the NF-κB/NLRP3/GSDMD-mediated pyroptotic pathway in both in vivo and in vitro settings. Conclusion. GPS exhibits neuroprotective effects in PD by suppressing microglia-mediated neuro-inflammation and pyroptosis, suggesting its potential as a favorable therapeutic agent for PD treatment
Open Access
Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Navone, Stefania Elena; Marfia, Giovanni; Giannoni, Amedeo; Beretta, Matteo; Guarnaccia, Laura; Gualtierotti, Roberta; Nicoli, Daniele; Rampini, Paolo; Campanella, Rolando
Intervertebral disc (IVD) degeneration (IDD) is one of the major causes of back pain, a condition that represents a serious socio-economic burden. Deeper knowledge of the complex and fine relationship between IVD degeneration, tissue inflammation and pain, appears to be critical to improve the current therapies, which have so far proven themselves ineffective. Upon degeneration, IVD tissues become inflamed, and this inflammatory microenvironment is associated with a cascade of degenerative events that may eventually cause discogenic pain. In particular, several studies have highlighted the major role of a number of proinflammatory mediators not only in the onset of the inflammatory condition, but also in the development of IDD in general. In this review, we will present the main pathological events that occur during disc degeneration, focusing on the relationship between the abnormal inflammatory milieu of the degenerating IVD, IDD and the generation of pain. Finally, we will present the current therapies for the treatment of IDD and low back pain, and the perspectives of future, more effective therapies.
Open Access
Interplay between metalloproteinases and cell signalling in blood brain barrier integrity
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Pla Navarro, Irene; Bevan, Damon; Hajihosseini, Mohammad K.; Lee, Martin; Gavrilovic, Jelena
The Blood-Brain Barrier (BBB) is a highly specialised interface separating the Central Nervous System (CNS) from circulating blood. Dysregulation of the BBB is a key early event in pathological conditions such as inflammation, in which the entry of activated leukocytes into the CNS is facilitated by BBB breakdown. The metzincin family of metalloproteinases (MPs) is one of the major contributors to BBB permeability as they cleave endothelial cell-cell contacts and underlying basal lamina components. However, the mechanisms by which MPs regulate BBB integrity has not yet been fully elucidated. The aim of this review is to provide an overview of pathways by which MPs could regulate the BBB in the context of neuroinflammation.
Open Access
Iron in the migraine brain
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Tepe, Nermin; Yemisci, Muge; Karatas, Hulya
Iron, a vital element for numerous peripheral and central nervous system functions, is a key player in DNA synthesis, gene expression, myelination, neurotransmission, and mitochondrial electron transport. Iron has utmost importance in various neurological functions, including neurotransmitter synthesis and brain cell metabolism. Migraine is a neurogliovascular disorder in which neuroinflammation plays a crucial role. Iron deficiency has been associated with various neurological issues and could potentially influence migraine frequency or severity. However, the relationship between iron levels and migraine is not fully clear and necessitates further research. On the other hand, iron overload could also have negative effects, as excessive iron might contribute to oxidative stress and inflammation, which may impact migraine-related pathways. The interplay between iron levels and neuroinflammation might affect migraines. While iron deficiency could exacerbate inflammation or disrupt neurotransmitter balance, iron overload might increase oxidative stress and neuroinflammation. Comprehending this balance is fundamental, as both iron deficiency and overload can have detrimental effects on brain health and migraine symptoms. In this review, we will summarize the current interconnection between migraine, iron levels, and neuroinflammation that are currently under active investigation
Open Access
Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Okada, Takeshi; Suzuki, Hidenori
Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder. Neuro- inflammation is a critical cause of brain injury following SAH in both acute and chronic phases. While accumulating evidence has shown that therapies targeting neuroinflammation exerted beneficial effects in experimental SAH, there is little clinical evidence. One of the factors making neuroinflammation complicated is that inflammatory signaling pathways and mediators act as protective or detrimental responses at different phases. In addition, biomarkers to detect neuro- inflammation are little known in clinical settings. In this review, first, we discuss how the inflammatory signaling pathways contribute to brain injury and other secondary pathophysiological changes in SAH. Damage-associated molecular patterns arising from mechanical stress, transient global cerebral ischemia, red blood cell breakdown and delayed cerebral ischemia following SAH trigger to activate pattern recognition receptors (PRRs) such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and receptors for advanced glycation end products. Most of PRRs activate common downstream signaling transcriptional factor nuclear factor-κΒ and mitogen-activated protein kinases, releasing pro-inflammatory mediators and cytokines. Next, we focus on how pro-inflammatory substances play a role during the course of SAH. Finally, we highlight an important inducer of neuroinflammation, matricellular protein (MCP). MCPs are a component of extracellular matrix and exert beneficial and harmful effects through binding to receptors, other matrix proteins, growth factors, and cytokines. Treatment targeting MCPs is being proved efficacious in pre- clinical models for preventing brain injury including neuroinflammation in SAH. In addition, MCPs may be a candidate of biomarkers predicting brain injury following SAH in clinical settings.
Open Access
Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) García, Sebastián; Martín Giménez, Virna Margarita; Mocayar Marón, Feres José; Reiter, Russel J.; Manucha, Walter
Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of "neuroinflammaging" has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuro- inflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson's and Alzheimer's diseases. Some of these neuroprotective effects are fundamentally related to its anti- inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.
Open Access
Microglia mediated neuroinflammation - signaling regulation and therapeutic considerations with special reference to some natural compounds
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Yao, Yue-yi; Ling, Eng-Ang; Lu, Di
Neuroinflammation plays a central role in multiple neurodegenerative diseases and neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebral ischemic injury etc. In this connection, microglia, the key players in the central nervous system, mediate the inflammatory response process. In brain injuries, activated microglia can clear the cellular debris and invading pathogens and release neurotrophic factors; however, prolonged microglia activation may cause neuronal death through excessive release of inflammatory mediators. Therefore, it is of paramount importance to understand the underlying molecular mechanisms of microglia activation to design an effective therapeutic strategy to alleviate neuronal injury. Recent studies have shown that some natural compounds and herbal extracts possess anti- inflammatory properties that may suppress microglial activation and ameliorate neuroinflammation and hence are neuroprotective. In this review, we will update some of the common signaling pathways that regulate microglia activation. Among the various signaling pathways, the Notch-1, mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain- enhancer of activated B cells (NF-κB) have been reported to exacerbate microglia mediated neuroinflammation that is implicated in different neuropathological diseases. The search for natural compounds or agents, specifically those derived from natural herbal extracts such as Gastrodin, scutellarin, Rg1 etc. has been the focus of many of our recent studies because they have been found to regulate microglia activation. The pharmacological effects of these agents and their potential mechanisms for regulating microglia activation are systematically reviewed here for a fuller understanding of their biochemical action and therapeutic potential for treatment of microglia mediated neuropathological diseases.
Open Access
Plexin-mediated neuronal development and neuroinflammatory responses in the nervous system
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Dai, Lu; Shen, Kai-Feng; Zhang, Chun-Qing
Plexins are a large family of single-pass transmembrane proteins that mediate semaphorin signaling in multiple systems. Plexins were originally characterized for their role modulating cytoskeletal activity to regulate axon guidance during nervous system development. Thereafter, different semaphorin-plexin complexes were identified in the nervous system that have diverse functions in neurons, astrocytes, glia, oligodendrocytes, and brain derived-tumor cells, providing unexpected but meaningful insights into the biological activities of this protein family. Here, we review the overall structure and relevant downstream signaling cascades of plexins. We consider the current knowledge regarding the function of semaphorin-plexin cascades in the nervous system, including the most recent data regarding their roles in neuronal development, neuroinflammation, and glioma.
Open Access
Quantification of photoreceptors’ changes in a diabetic retinopathy model with two-photon imaging microscopy
(MDPI, 2024-08-11) Bautista-Elivar, Nazario; Avilés Trigueros, Marcelino; Bueno García, Juan Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y Optometría
Emerging evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR), preceding the development of microvascular abnormalities. Here, we assessed the impact of neuroinflammation on the retina of diabetic-induced rats. For this aim we have used a two-photon microscope to image the photoreceptors (PRs) at different eccentricities in unstained retinas obtained from both control (N = 4) and pathological rats (N = 4). This technique provides high-resolution images where individual PRs can be identified. Within each image, every PR was located, and its transversal area was measured and used as an objective parameter of neuroinflammation. In control samples, the size of the PRs hardly changed with retinal eccentricity. On the opposite end, diabetic retinas presented larger PR transversal sections. The ratio of PRs suffering from neuroinflammation was not uniform across the retina. Moreover, the maximum anatomical resolving power (in cycles/deg) was also calculated. This presents a double-slope pattern (from the central retina towards the periphery) in both types of specimens, although the values for diabetic retinas were significantly lower across all retinal locations. The results show that chronic retinal inflammation due to diabetes leads to an increase in PR transversal size. These changes are not uniform and depend on the retinal location. Two-photon microscopy is a useful tool to accurately characterize and quantify PR inflammatory processes and retinal alterations.
Open Access
Regulation of inflammatory cytokines for spinal cord injury recovery
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Lin, Sen; Xu, Chang; Lin, Jiaquan; Hu, Hengshuo; Zhang, Chuanjie; Mei, Xifan
Spinal cord injury (SCI) is one of the most destructive traumatic diseases in human beings. The balance of inflammation in the microenvironment is crucial to the repair process of spinal cord injury. Inflammatory cytokines are direct mediators of local lesion inflammation and affect the prognosis of spinal cord injury to varying degrees. In spinal cord injury models, some inflammatory cytokines are beneficial for spinal cord repair, while others are harmful. A large number of animal studies have shown that local targeted administration can effectively regulate the secretion and delivery of inflammatory cytokines and promote the repair of spinal cord injury. In addition, many clinical studies have shown that drugs can promote the repair of spinal cord injury by regulating the content of inflammatory cytokines. However, topical administration affects only a small portion of inflammatory cytokines. In addition, different individuals have different inflammatory cytokine profiles during spinal cord injury. Therefore, future research should aim to develop a personalized local delivery therapeutic cocktail strategy to effectively and accurately regulate inflammation and obtain substantial functional recovery from spinal cord injury
Open Access
Study of the link between neuronal death, glial response, and MAPK pathway in old parkinsonian mice
(Frontiers Media, 2020-07-29) Cuenca-Bermejo L,; Gallo-Soljancic P,; Sanchez-Rodrigo C,; Izura V,; Steinbusch HWM,; Fernandez-Villalba E,; Herrero MT; Cuenca Bermejo, Lorena; Gallo-Soljancic, Pablo; Sanchez-Rodrigo, Consuelo; Izura, Virginia; Steinbusch, Harry W. M.; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Gil Martínez, Ana Luisa; Medicina Interna; Facultad de Medicina
Parkinson's disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets. Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication. Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the p-ERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication. Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.
Open Access
Systemic inflammation aggravates retinal ganglion cell vulnerability to optic nerve trauma in adult rats
(MDPI, 2026-02-03) Rovere, Giuseppe ; Caja Matas, Yolanda; Vidal Villegas, Beatriz; Bernal Garro, José M. ; Sobrado Calvo, Paloma; Salinas Navarro, Manuel Ángel; Nucci, Carlo; Villegas Pérez, Maria Paz; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
Systemic inflammation is increasingly recognized as a modifier of neurodegenerative outcomes in the central nervous system; however, its impact on retinal ganglion cell (RGC) survival and retinal microglial responses following optic nerve (ON) injury in vivo remains incompletely understood. In this study, we investigated how systemic lipopolysaccharide (LPS)-induced inflammation influences retinal microglial activation and RGC vulnerability under physiological conditions and after traumatic ON damage. In adult female rats, systemic LPS administration by intraperitoneal injection induced rapid and robust microglial activation, characterized by process retraction and soma hypertrophy within hours and promoting microglial proliferation at later stages but without causing RGC loss in intact retinas. Following ON crush, systemic inflammation did not affect early RGC degeneration but significantly exacerbated neuronal loss during the late acute phase. This increased vulnerability was accompanied by a marked rise in microglial density and a pronounced redistribution of microglia toward the central retina and the ON head, a region of heightened anatomical and metabolic susceptibility. Together, these findings demonstrate that, in rats, systemic inflammation alone is insufficient to induce RGC degeneration but acts as a potent priming factor that amplifies neurodegeneration in the context of axonal injury. The temporal and spatial specificity of microglial responses underscores their context-dependent role in retinal pathology and identifies systemic inflammatory status as a critical determinant of retinal outcome after trauma. Targeted, time-dependent modulation of microglial activation may therefore represent a promising therapeutic strategy for optic neuropathies.
Open Access
Therapeutic effects of herbal compounds in cerebral ischemia with special reference to suppression of microglia activation implicated in neurodegeneration
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Jia, Wen Ji; Yuan, Yun; Wu, Chun Yun
Cerebral ischemia affects many especially with the ageing population. The ensuing ischemic reactions include oxidative stress, inflammation, and excitotoxicity among others. In the search for effective therapeutic strategies for cerebral ischemia, activated microglia which are the key player in neuroinflammation are now recognized as a potential therapeutic target. Microglia possess both neurotoxic and neuroprotective roles. They are protective by continuously surveilling the microenvironment, phagocytosing dead cells, secreting trophic factors and sculpting the neuronal connections by removing axons and pruning excess synapses. On the other hand, hyperactivated microglia may impair cerebral oxidative metabolism, and produce excessive proinflammatory mediators that may exacerbate the brain damage. In view of this, suppression of microglial activation has been considered a therapeutic strategy to mitigate microglia-based neuroinflammation in cerebral ischemia. However, balancing the neuroprotective and neurotoxic roles of activated microglia remains a challenging issue. Many traditional Chinese herbal agents have been used in clinic for treatment of cerebral ischemia. Here, we provide an overview of five common Chinese herbs targeting specifically microglia-mediated neuroinflammation in cerebral ischemia. It is hoped that a common parallel may be drawn from their beneficial effects especially in the latter pathological conditions for their better and effective use in the future.
Open Access
Unexpected exacerbation of neuroinflammatory response after a combined therapy in old parkinsonian mice
(Frontiers Media, 2018-11-30) Gil Martínez, Ana Luisa; Cuenca Bermejo, Lorena; Estrada, Cristina; Sánchez Rodrigo, Consuelo; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología; Ingeniería de la Información y las Comunicaciones; Facultades de la UMU::Facultad de Medicina
The design of therapeutic strategies that focus on the repositioning of anti-inflammatory and antioxidant drugs are a great bet to slow down the progression of neurodegenerative disorders. Despite the fact that Parkinson’s disease (PD) is an age-related pathology, almost all experimental studies are carried out in young animals. Here, we evaluated the possible neuroprotective effect of the combination of the antioxidant N-acetylcysteine (NAC) and the anti-inflammatory HA-1077 in aged 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (C57BL/6 mice, 20 months old), whose individual treatment has been shown to have neuroprotective effects in this Parkinsonism model. Interestingly, NAC+HA-1077-based treatment produced a significant increase in dopaminergic neuronal death accompanied by an increase in microglial and astroglial activation in the Substantia Nigra pars compacta (SNpc) and striatum of old-Parkinsonian mice compared to their control group. The astroglial response was also explored by co-immunostaining for GFAP and S100b together with p-JNK and it was found to be particularly exacerbated in the MPTP+NAC+HA-1077 group. The unexpected toxic effects found in the combined use of NAC and HA-1077 in old-Parkinsonian mice highlight the importance of taking into account that in elderly Parkinsonian patients the combination of some drugs (most of them used for other different age-related alterations) can have side effects that may result in the exacerbation of the neurodegenerative process.

Browsing by Subject "Neuroinflammation"

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