DigitalUM :: Browsing by Subject "Microglia"

Browsing by Subject "Microglia"

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Open Access
Activating Akt and the brain’s resources to drive cellular survival and prevent inflammatory injury
(Murcia : F. Hernández, 2005) Chong, Z.Z.; Li, F.; Maiese, K.
Protein kinase B, also known as Akt, is a serine/threonine kinase and plays a critical role in the modulation of cell development, growth, and survival. Interestingly, Akt is ubiquitously expressed throughout the body, but its expression in the nervous system is substantially up-regulated during cellular stress, suggesting a more expansive role for Akt in the nervous system that may involve cellular protection. In this regard, a body of recent work has identified a robust capacity for Akt and its downstream substrates to foster both neuronal and vascular survival during apoptotic injury. Cell survival by Akt is driven by the modulation of both intrinsic cellular pathways that oversee genomic DNA integrity and extrinsic mechanisms that control inflammatory microglial activation. A series of distinct pathways are regulated by Akt that include the Forkhead family of transcription factors, GSK-3ß, ß-catenin, c- Jun, CREB, Bad, IKK, and p53. Culminating below these substrates of Akt are the control of caspase mediated pathways that promote genomic integrity as well as prevent inflammatory cell demise. With further levels of progress in defining the cellular role of Akt, the attractiveness of Akt as a vital and broad cytoprotectant for both neuronal and vascular cell populations should continue to escalate.
Open Access
Alternate approach to understanding the molecular mechanisms of stroke-induced injury
(Murcia : F. Hernández, 2007) Willing, A.E.; Pennypacker, K.
Research in the area of stroke has not yielded any new treatments, besides tissue plasminogen activator. New findings are suggesting that the therapeutic window of providing neuroprotection is wider than once thought. Moreover, the role of the peripheral immune system in abetting neurodegeneration is being elucidated, but it appears this reaction occurs 2- 3 days after the stroke. This mini-review examines this new evidence about the molecular mechanisms leading to stroke-induced neuronal death, which suggests new therapeutic approaches to its treatment.
Open Access
An electron microscopic study of neuronal degeneration and glial cell reaction in the retina of glaucomatous rats
(Murcia : F. Hernández, 2002) Wang, X.; Tay, S.S.W.; Ng, Y.K.
The present investigation was focused on the ultrastructural changes in the neurons and glial cells in the retina of rats with experimentally-induced glaucoma. An experimental glaucoma model was created by limbal-derived vein cauterization. Animals were sacrificed at 1, 3 weeks and 3 months post-operation. Retinae were dissected and processed for electron microscopy. Neuronal degeneration was observed in all the different layers of the retina at both 1 and 3 weeks post-operation. Some degenerating neurons were found in the ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL). And the dying neurons presented apoptotic-like more than necrotic neurons. Many degenerating axons and axon terminals were observed between neurons in the GCL, inner plexiform layer (IPL), INL, and outer plexiform layer (OPL). Activated astrocytes and microglial cells were present in close association with degenerating neurons and axons. The Müller cells in the INL also presented longer and darker processes with more microfilaments than in normal cells. Degenerating neuronal debris, degenerating axonal profiles and electron-dense bodies were often found in the cytoplasm of macrophages. The results suggest that both microglial cells and astrocytes are activated in the process of neuronal degeneration in the retina of experimentally-induced glaucomatous rats. It is hypothesized that they may play a protective role in removing degenerating neuronal elements in the retina after the onset of glaucoma.
Restricted
Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension
(Elsevier, 2018-03-09) Hoz, Rosa de; Ramírez, Ana I.; González Martín, Rosa; Ajoy, Daniel; Rojas, Blanca; Salobrar García, Elena; Valiente Soriano, Francisco J.; Avilés Trigueros, Marcelino; Villegas Pérez, María P.; Vidal Sanz, Manuel; Triviño, Alberto; Ramírez, José M.; Salazar, Juan J.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
The immune system plays an important role in glaucomatous neurodegeneration. Retinal microglial reactivation associated with ganglion cell loss could reportedly contribute to the glaucoma progression. Recently we have described signs of microglia activation both in contralateral and ocular hypertension (OHT) eyes involving all retinal layers 15 days after OHT laser induction in mice. However, no works available have analyzed the microglial activation at earliest time points after OHT induction (24 h) in this experimental model. Thus, we seek to describe and quantify signs of microglia activation and differences depending on the retinal layer, 24 h after unilateral laser-induced OHT. Two groups of adult Swiss mice were used: age-matched control (naïve) and lasered. In the lasered animals, OHT eyes as well as contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1 and MHC-II. We quantified the number of microglial cells in the photoreceptor layer (OS), outer plexiform layer (OPL), and inner plexiform layer (IPL); the number of microglial vertical processes connecting the OPL and OS; the area of the retina occupied by Iba-1+ cells (Iba1-RA) in the nerve fiber layer-ganglion cell layer (NFL-GCL), the total arbor area of microglial cells in the OPL and IPL and; Iba-1+ cell body area in the OPL, IPL and NFL-GCL. In contralateral and OHT eyes the morphological features of Iba-1+ cell activation were: migration, enlargement of the cell body, higher degree of branching and reorientation of the processes, radial disposition of the soma and processes toward adjacent microglial plexuses, and presence of amoeboid cells acting as macrophages. These signs were more pronounced in OHT eyes. Most of Iba-1+ cells did not express MHC-II; rather, only dendritic and rounded cells expressed it. In comparison with naïve eyes, in OHT eyes and contralateral eyes no significant differences were found in the microglial cell number; but there was a significant increase in Iba1-RA. The total arbor area of microglial cells was significantly decreased in: i) OHT eyes with respect contralateral eyes and naïve-eyes in IPL; ii) OHT eyes with respect to naïve eyes in OPL. The number of microglial vertical processes connecting the OPL and OS were significantly increased in contralateral eyes compared with naïve-eyes and OHT eyes. In OPL, IPL and NFL-GCL, the cell body area of Iba-1+ cells was significantly greater in OHT eyes than in naïve and contralateral eyes, and greater in contralateral eyes than in naïve eyes. A non-proliferative microglial reactivation was detected both in contralateral eyes and in OHT eyes in an early time after unilateral laser-induced OHT (24 h). This fast microglial activation, which involves the contralateral eye, could be mediated by the immune system.
Open Access
Comparison of MR images and histochemical localization of intra-arterially administered microglia surrounding ß-amyloid deposits in the rat brain
(Murcia : F. Hernández, 2006) Song, Y.; Morikawa, S.; Morita, M.; Inubushi, T.; Takada, T.; Torii, R.; Kitamura, Y.; Taniguchi, T.; Tooyama, I.
The therapeutic use of microglial cells has recently received some attention for the treatment of Alzheimer disease (AD), but few non-invasive techniques exist for monitoring the cells after administration. Here we present a magnetic resonance imaging (MRI) technique for tracking microglia injected intra-arterially in vivo. We micro-injected Aß42 into the left hippocampus and saline into the right hippocampus of rats. We then administered microglia, which were labeled with enhanced green fluorescent protein (EGFP) gene and Resovist, into the carotid artery. After monitoring exogenously administered microglia using MRI, we compared the MR images and the histochemical localization of administered microglia. MRI revealed clear signal changes attributable to Resovist-containing microglia in Aß-injected areas. Histochemistry demonstrated that EGFP-positive microglia accumulated around Aß deposits and internalized the peptide. This study demonstrates the usefulness of MRI for non-invasive monitoring of exogenous microglia, and suggests a promising future for microglia/macrophages as therapeutic tools for AD.
Open Access
De novo expression of the hemoglobin scavenger receptor CD163 by activated microglia is not associated with hemorrhages in human brain lesions
(Editores F. Hernandez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologia, 2011) Holfelder, K.; Schittenhelm, J.; Trautmann, K.; Haybaeck, J.; Meyermann, R.; Beschorner, R.
The main function of CD163 (hemoglobin scavenger receptor) is to bind the hemoglobinhaptoglobin complex, thereby mediating extravasal hemolysis. However, CD163 also has an antiinflammatory function. After CD163-mediated endocytosis, hemoglobin is catabolized further by hemeoxygenase 1 (HO-1). Previously, we found expression of HO-1 to be restricted to microglia/ macrophages at sites of hemorrhages in human traumatic and ischemic brain lesions. We now investigated if CD163 expression is also correlated with hemorrhages in brain lesions. Methods. Autopsy brain tissue from 44 cases with hemorrhagic brain lesions (32 traumatic brain injuries/TBI, 12 intracerebral bleedings/ICB), 56 nonhemorrhagic brain lesions (30 ischemias, 26 hypoxias) and 6 control brains were investigated. The post injury survival times ranged from a few minutes to 60 months. Results. In controls, single perivascular monocytes expressed CD163, but only single CD163+ microglia were found in 3/6 cases. CD163+ cells in the parenchyma (activated microglia/macrophages) increased significantly within 24 hours after trauma and ischemia and within 1-7 days following ICB or hypoxia. Overall, significantly lower and higher levels of parenchymal CD163+ cells occurred in hypoxia and ischemia, respectively. Perivascular CD163+ cells also increased significantly in all pathological conditions. In areas remote from circumscribed brain lesions (TBI, ICB, ischemia), significant changes were only found in ICB and ischemia. Conclusions. De novo expression of CD163 by activated microglia/macrophages and CD163+ infiltrating monocytes are neither restricted to nor predominant in hemorrhagic brain lesions. Thus, the antiinflammatory function of CD163 probably predominates, both in hemorrhagic and non-hemorrhagic brain lesions and points to possible immunomodulatory treatment strategies targeting CD163
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
Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Grković, Ivana; Mitrović, Nataša; Dragić, Milorad; Kontić, Marina Zarić
Adenosine 5'-triphosphate (ATP) and other nucleotides and nucleosides, such as adenosine, are versatile signaling molecules involved in many physiological processes and pathological conditions in the nervous system, especially those with an inflammatory component. They can be released from nerve cells, glial cells, and vascular cells into the extracellular space where they exert their function via ionotropic (P2X) or metabotropic (P2Y) receptors. Signaling via extracellular nucleotides and adenosine is regulated by cell-surface located enzymes ectonucleotidases that hydrolyze the nucleotide to the respective nucleoside. This review summarizes a histochemical approach for detection of ectonucleotidase activities in the cryo-sections of brain tissue. The enzyme histochemistry (EHC) might be used as suitable replacement for immunohistochemistry, since it gives information about both localization and activity, thus adding a functional component to a classical histological approach. With this technique, it is possible to visualize spatial distribution and cell-specific localization of ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (eN/CD73) activities during brain development, after different hormonal manipulations, during neurodegeneration, etc. EHC is also suitable for investigation of microglial morphology in different (patho)physiological conditions. Furthermore, the review describes how to quantify EHC results.
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
Hippocampal expressions of metallothionein I/II and glycoprotein 96 in EAE-prone and EAE-resistant strains of rats
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Grubić Kezele, Tanja; Blagojević Zagorac, Gordana; Jakovac, Hrvoje; Domitrović, Robert; Radošević Stašić, Biserka
Inflammatory demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are often followed by cognitive deficits associated with the neuronal injury, synaptic loss and altered neurogenesis within the hippocampus. Changes depend on the genetic and epigenetic factors that ensure the cellular and environmental homeostasis and regulate the interactions of immunocompetent, glial and neural cells. Owing to high impact of stress proteins on these processes, in this study we compared the protein content of interleukin-6, transforming growth factor-β1, metallothioneins I/II (MTs) and glycoprotein 96 (gp96) in the hippocampus of DA and AO rats that differ in the susceptibility to the induction of EAE, and tested the relationship of MTs and gp96 to granule neurons, glial cells and neural progenitors in different subfields of dentate gyrus. Rats were immunized with bovine brain homogenate emulsified in complete Freund’s adjuvant or only with CFA. The data showed that acute attack of EAE in DA rats was followed by accumulation of IL-6, TGF-β1 and MTs proteins, by increased expression of MTs in molecular and granular cell layer, by reduced expression of gp96/granular cell, by apoptosis and by microgliosis with appearance of Iba-1+ cells, co-expressing MT I/II and gp96. Furthermore, in subgranular zone (SGZ) of DA rats an augmented number of GFAP+ precursors, but decreased number of doublecortin (DCX)+ neuroblasts and immature NeuN+ neurons were found, implying that in DA rats the neurogenesis was delayed or reduced. Besides, in SGZ of both strains several DCX+ and NeuN+ cells co-expressing gp96 and MT I/II were found.
Open Access
Lectinhistochemistry and ultrastructure of microglial response to monosodium glutamate-mediated neurotoxicity in the arcuate nucleus
(Murcia : F. Hernández, 1999) Pelaez, B.; Blazquez, J.L.; Pastor, F.E.; Sánchez, A.; Amat, P.
In this study we describe the most relevant morphological features of the microglial reaction that takes place in the arcuate nucleus (AN) after neurotoxic injury induced by a single subcutaneous injection of monosodium glutamate (MSG) in neonatal rats. The time course of the reaction was evaluated by lectinhistochemistry. Microglial/macrophagic cells were labelled with the lectin obtained from Lycopersicon esculentum and with B4 isolectin from Griffonia simplicifolia. The microglial response was also studied by ultrastructural observations. 'The histochemical study revealed the presence of few reactive microglial cells at 6 h post-injection. These cells were intensely stained and had a globular morphology but contained no neuronal debris inside them when observed under the electron microscope. At 12 h post-injection, the number of microglial cells had increased and, at the same time, intense phagocytic activity was observed ultrastructurally. The microglial reaction peaked at 24 and 36 h post-injection, when the number of microglial/ macrophagic cells was maximum, although the ultrastructural observations showed that at 36 h the amount of debris ingested by macrophages was decreased with respect to animals sacrificed at 24 h. Finally, at 4 days after neurotoxic injection the number and morphology of microglial cells were similar to those observed in the control rats. The ultrastructural study also revealed the existence of microglial cell mitosis in the territory of the AN together with a strong increase in the number of supraependymal cells resembling macrophages in the third ventricle during the lesion. Our data demonstrate that activated microglial cells initially extend throughout the damaged territory, but from 24-36 h onwards they are especially patent in the ventrolateral portions of the AN.
Open Access
Maternal undernutrition model of two generations of rats: Changes in the aged retina
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Laurinaviciute, Guoda; Simkunaite-Rizgeliene, R.; Zalgeviciene, V.; Cepuliene, R.; Jakimaviciene, E.M.; Galgauskas, S.; Petroska, D.; Besusparis, J.; Tutkuviene, J.
The impact of maternal undernutrition on morphological changes of the retina was assessed in two generations of aged offspring. Wistar 18 rats (9 of each generation of 20-month-old female offspring; in total -27 eyes) were analyzed. The first generation offspring were born to mothers who: (a) were restricted to food only before pregnancy (pre-pregnancy); (b) whose food was restricted before and during pregnancy. The control group and all the offspring were fed normally. After enucleating the eyes, paraffin sections were stained with hematoxylin and eosin. The thickness of retina layers was measured. Cryosections were immunostained using glial fibrillary acidic protein, ionized calcium-binding adaptor molecule1, RNA-binding protein with multiple splicing for evaluation of macroglia, microglia and retinal ganglion cells by digital image analysis tools. Our data have shown atrophy of photoreceptor layer and degeneration of outer nuclear layer in all investigated groups, but less damage was found in the control group. Higher Müller cell activity and greater number of microglial cells was observed in the second generation offspring born from both restricted diet groups. Higher numbers of microglial and retinal ganglion cells were observed in the second generation in comparison to the first generation offspring. Malnutrition of the mother may be one of the possible causes of degeneration of the outer layers of the retina and activation of Müller cells in the second generation offspring. The effect of maternal nutritional restriction on the number of microglial and retinal ganglion cells is unclear
Open Access
Median nerve electrical stimulation improves traumatic brain injury by reducing TACR1 to inhibit nuclear factor-κB and CCL7 activation in microglia
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Sun, Fan; Li, Xiaodong; Wang, Xiao-Wei; Ou, Yali; Li, Xuesong; Shi, Min
The existing report elucidates that median nerve electrical stimulation (MNS) plays a role in treating traumatic brain injury (TBI). Herein, we explored the mechanism of MNS in TBI. A TBI-induced coma model (skull was hit by a cylindrical impact hammer) was established in adult Sprague-Dawley rats. Microglia were isolated from newborn Sprague-Dawley rats and was injured by lipopolysaccharide (LPS; 10 ng/mL). Consciousness was assessed by sensory and motor functions. Brain tissue morphology was detected using hematoxylin-eosin staining assay. Ionized calcium binding adapter molecule 1, NeuN and tachykinin receptor 1 (TACR1) level were detected by immunohistochemical assay. Levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme linked immune sorbent assay (ELISA). Levels of TACR1, C-C motif chemokine ligand 7 (CCL7), phosphorylation (p)-P65 and P65 were assessed by quantitative real time polymerase chain reaction (qRT-PCR) and western blot. M1 markers (inducible nitric oxide synthase and CD86) and M2 markers (arginase-1 (Arg1) and chitinase 3-like 3 (YM1)) of microglia as well as the transfection efficiency of short hairpin TACR1 (shTACR1) were assessed by qRT-PCR. Immunofluorescence and flow cytometry assay were used to detect microglia morphology and neuron apoptosis. MNS reduced neuron injury and microglia activation in the TBI-induced rat coma model. MNS reversed the effects of TBI on levels of inflammation-related factors, M1/M2 microglia markers, TACR1, p-P65/P65 and CCL7 in rats. shTACR1 reversed the effects of LPS on inflammation-related factors, M1/M2 microglia markers, microglia activation, neuron apoptosis, p-P65/P65 value and CCL7 level. Our results revealed that MNS improved TBI by reducing TACR1 to inhibit nuclear factor-κB (NF-κB) and CCL7 activation in microglia.
Open Access
Microglia and prion disease, a review
(Murcia : F. Hernández, 1997) Brown, D.R.; Kretzschrnar, H.A.
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Open Access
Morphological changes in microglia in the mouse brain during postnatal development and obesity
(2026) Chu Zhang; Ge Gao; Xiaonan Shao; YJing Kang; Xin Yan; Juntang Lin; Liang Qiao; Yang Li1; Biología Celular e Histología
Microglia are innate immune cells in the central nervous system (CNS) and play critical roles in proper brain development and function. During postnatal development, microglia have a highly plastic morphology and change rapidly in response to the temporal brain environment. However, their dynamics and phenotypes during this period are still not fully elucidated. Here, we systematically elucidated microglial density and morphological changes during postnatal development as well as in pathological obese conditions. Our results demonstrated a spatiotemporal distribution of microglia in different brain regions associated with gradually increased microglial complexity during postnatal development. Moreover, microglia become reactive in most brain regions of obese mice, but their morphological diversity has a region-specific manner, with an obvious alteration in the hypothalamus. Overall, our data emphasized the morphological dynamics of microglia following developing time windows and provided the basic information for future investigations.
Open Access
Phosphorylated TDP-43 localizes to chronic cerebral infarctions in human brains
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Umahara, Takahiko; Uchihara, Toshiki; Hirao, Kentaro; Shimizu, Soichiro; Hanyu, Haruo
The transactivation response DNA-binding protein of 43 kDa (TDP-43) is a nuclear protein pivotal in RNA processing. Because phosphorylated TDP43 (pTDP-43) has been identified as a component of the ubiquitin-positive and tau-negative inclusions observed in the brains of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients, it is considered to play a major role in neurodegenerative processes. We previously reported that pTDP-43 is located in macrophages of atherosclerotic lesions of human carotid and major cerebral arteries. We hence hypothesized that pTDP-43 might be localized in the macrophages of other human brain lesions. Therefore, we investigated the immunolocalization of pTDP-43 in human brains with chronic cerebral infarction. Furthermore, we investigated the colocalization of pTDP-43 and the 14-3-3 eta isoform and found that pTDP-43 was localized in many macrophages located in chronic cerebral infarctions, in 6 out of the 15 human brains analyzed. pTDP-43 colocalized with the 14-3-3 eta isoform in these lesions. This is the first demonstration of pTDP-43 immunolocalization in chronic cerebral infarctions in human brains. We believe that our findings may be useful towards further understanding the pathophysiological roles of TDP-43 in various neurological disorders.
Open Access
Qualitative evaluations of reactive microglial heterogeneity in cultured porcine retina
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Johansson, Kjell; Mohlin, Camilla
A late stage of several retinal disorders is retinal detachment, a complication that results in rapid photoreceptor degeneration and synaptic damage. The porcine retina is a favorable in vitro model for studies of the degenerative processes that follow retinal detachment. Photoreceptor degeneration and synaptic injuries develop rapidly in the cultured porcine retina and correlate with resident microglial cell transition into a reactive phenotype. In this in vitro study, we used retinas cultured for five days and analyzed reactive CD11b and Iba1 immunoreactive microglia that localized close to/within the synaptic outer plexiform layer (OPL) and in the outer nuclear layer (ONL). A subpopulation of the CD11b and Iba1immunoreactive microglia also expressed CD68 immunoreactivity on lysosomal membranes or as a diffuse cytoplasmic stain. Some CD68 immunoreactive microglia were juxtaposed to L/M-opsin immunoreactive cone photoreceptors in the ONL. CD11b and Iba immunoelectron microscopy further suggests the presence of a dark microglial phenotype in the degenerating cultured porcine retina. For immunoelectron microscopy, nickel-enhanced diaminobenzidine (DAB) staining resulted in clearly distinguished reaction products in the cytosol of dark microglia
Open Access
Rapid microglial activation induced by traumatic brain injury is independent of blood brain barrier disruption
(Murcia : F. Hernández, 2007) Koshinaga, M.; Suma, T.; Fukushima, M.; Tsuboi, I.; Aizawa, S.; Katayama, Y.
Following CNS injury, microglia respond and transform into reactive species exhibiting characteristic morphological changes that have been termed “activated” or “ameboid” microglia. In an attempt to establish that microglial reactions induced immediately after injury are caused by intrinsic mechanisms rather than infiltration of blood and its constituents, oxygenized Ringer’s solution was perfused into the cerebral circulation of rats so that the circulating blood could be eliminated prior to injury induction. Under artificial respiration, a catheter was inserted from the cardiac apex into the ascending aorta, and oxygenized Ringer’s solution was immediately perfused with a pulsatile blood pump, resulting in wash out of the circulating blood from the brain within 1 min. Subsequently, a cortical contusion was induced in the unilateral parietal cortex using a controlled cortical impact (CCI) device. At 5 min following the injury, the brain was fixed by perfusion of fixative through the catheter and removed. Coronal vibratome sections were then processed for CR3 immunohistochemistry to examine the microglial activation. It appeared that microglial activation with both morphological transformation and an increase in CR3 immunoreactivity was induced throughout the hemisphere ipsilateral to the injury side exclusively, even in rats with elimination of circulating blood. The microglial reactions did not differ substantially from those observed in the control rats with extensive BBB disruption. The present results thus provide direct evidence that the microglial activation induced immediately after injury is independent of infiltration of circulating blood induced by concurrent BBB disruption.
Open Access
The aging rat retina: from function to anatomy
(Elsevier, 2018-01-01) Nadal-Nicolás, Francisco Manuel; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
In healthy beings, age is the ultimate reason of cellular malfunction and death. In the rat retina, age causes a functional decline and loss of specific neuronal populations. In this regard, controversial conclusions have been reported for the innermost retina. Here, we have studied the albino and pigmented retina for the duration of the rat life-span. Independent of age (21 dayse22 months), the electroretinographic recordings and the volume of the retina and its layers are smaller in albinos. Functionally, aging causes in both strains a loss of cone- and rod-mediated responses. Anatomically, cell density decreases with age because the retina grows linearly with time; no cell loss is observed in the ganglion cell layer; and only in the pigmented rat, there is a decrease in cone photoreceptors. In old animals of both strains, there is gliosis in the superior colliculi and a diminution of the area innervated by retinal ganglion cells. In conclusion, this work provides the basis for further studies linking senescence to neurodegenerative retinal diseases.
Open Access
The application of mesenchymal stem cells in the treatment of traumatic brain injury: Mechanisms, results, and problems
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhang, Ying; Zheng, Zejun; Sun, Jinmeng; Xu, Shuangshuang; Wei, Yanan; Ding, Xiaoling; Ding, Gang
Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be derived from a wide variety of human tissues and organs. They can differentiate into a variety of cell types, including osteoblasts, adipocytes, and chondrocytes, and thus show great potential in regenerative medicine. Traumatic brain injury (TBI) is an organic injury to brain tissue with a high rate of disability and death caused by an external impact or concussive force acting directly or indirectly on the head. The current treatment of TBI mainly includes symptomatic, pharmacological, and rehabilitation treatment. Although some efficacy has been achieved, the definitive recovery effect on neural tissue is still limited. Recent studies have shown that MSC therapies are more effective than traditional treatment strategies due to their strong multi-directional differentiation potential, self-renewal capacity, and low immunogenicity and homing properties, thus MSCs are considered to play an important role and are an ideal cell for the treatment of injurious diseases, including TBI. In this paper, we systematically reviewed the role and mechanisms of MSCs and MSC-derived exosomes in the treatment of TBI, thereby providing new insights into the clinical applications of MSCs and MSC-derived exosomes in the treatment of central nervous system disorders