Galectin-3 is upregulated in microglial cells in response to ischemic brain lesions, but not to facial nerve axotomy

Walther, Michael; Kuklinski, Stephan; Pesheva, Penka; Guntinas‐Lichius, Orlando; Angelov, Doychin N.; Neiss, Wolfram F.; Asou, Hiroaki; Probstmeier, Rainer

doi:10.1002/1097-4547(20000815)61:4<430::aid-jnr9>3.0.co;2-3

Cited by 84 publications

(52 citation statements)

References 32 publications

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“…The photothrombotic focal stroke method was performed as first described by Watson et al (1985), and is usually modified to allow for differences in laser efficiency, and rose bengal delivery in different strains of mice. In brief, mice were anesthetized in an induction chamber ventilated with 5% isoflurane gas, and then transferred to a stereotaxic frame and maintained at 1.5% isoflurane using a nose mask.…”

Section: Methodsmentioning

confidence: 99%

“…For mice analyzed at 7 d post injury (DPI), every fourth slide (minimum of 10 sections) through the lesion was tested to create an accurate sample of the injury, and stained by immunofluorescence for microglia (Iba-1 or GFP) and astrocytes (GFAP). Area of injury was outlined and measured using ImageJ software (Zhang et al, 2010), and compared with cortical volume on the contralateral side within the same section. Thirty-two days after stroke, every second slide was Nissl stained throughout the lesion and imaged with bright-field microscopy, in addition to imaging and analyzing the area occupied by GFPϩ microglia in the CX3CR1-GFP transgenic mouse crosses.…”

Section: Infarct Volume Measurementmentioning

confidence: 99%

“…Thirty-two days after stroke, every second slide was Nissl stained throughout the lesion and imaged with bright-field microscopy, in addition to imaging and analyzing the area occupied by GFPϩ microglia in the CX3CR1-GFP transgenic mouse crosses. The area of injury was outlined and measured using ImageJ software (Zhang et al, 2010) and the volume of the lesion was determined with the following formula: mean area of lesion ϫ distance between sections ϫ number of sections, as described by Clark et al (2008).…”

Section: Infarct Volume Measurementmentioning

confidence: 99%

“…1-3), including upregulation of Iba-1 and galectin-3 (Gal-3). Gal-3 is a 30 kDa ␤-galactosidase-binding lectin that is upregulated by reactive microglia and macrophages following ischemia (Walther et al, 2000;Yan et al, 2009). Gal-3 is not detected in ramified microglia in the uninjured cerebral cortex (Fig.…”

Section: Sparc-null Mice Show Increased Microgliosis and Enhanced Funmentioning

confidence: 99%

“…To specifically test if SPARC can regulate neuroimmune responses independent of transplantation, here we used a focal photothrombotic cortical stroke lesion (Watson et al, 1985) and an NMDA-induced excitotoxic lesion. Ischemic stroke causes neuronal cell death and associated disability (Moskowitz et al, 2010), and the response to this and excitotoxic challenge involves multiple glia, including an inflammatory response by microglia and formation of a glial scar by activated astrocytes (Iadecola and Anrather, 2011).…”

Section: Introductionmentioning

confidence: 99%

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SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia

et al. 2013

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Secreted protein acidic rich in cysteine (SPARC) is a matricellular protein that modulates the activity of growth factors, cytokines, and extracellular matrix to play multiple roles in tissue development and repair, such as cellular adhesion, migration, and proliferation. Throughout the CNS, SPARC is highly localized in mature ramified microglia, but its role in microglia-in development or during response to disease or injury-is not understood. In the postnatal brain, immature amoeboid myeloid precursors only induce SPARC expression after they cease proliferation and migration, and transform into mature, ramified resting microglia. SPARC null/CX3CR1-GFP reporter mice reveal that SPARC regulates the distribution and branching of mature microglia, with significant differences between cortical gray and white matter in both controls and SPARC nulls. Following ischemic and excitotoxic lesion, reactive, hypertrophic microglia rapidly downregulate and release SPARC at the lesion, concomitant with reactive, hypertrophic perilesion astrocytes upregulating SPARC. After photothrombotic stroke in the forelimb sensorimotor cortex, SPARC nulls demonstrate enhanced microgliosis in and around the lesion site, which accompanies significantly enhanced functional recovery by 32 d after lesion. Microglia from SPARC nulls also intrinsically proliferate at a greater rate in vitro-an enhanced effect that can be rescued by the addition of exogenous SPARC. SPARC is thus a novel regulator of microglial proliferation and structure, and, in addition to regulating glioma progression, may play an important role in differently regulating the gray and white matter microglial responses to CNS lesion-and modulating behavioral recovery-after injury.

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Section: Methodsmentioning

confidence: 99%

Section: Infarct Volume Measurementmentioning

confidence: 99%

Section: Infarct Volume Measurementmentioning

confidence: 99%

Section: Sparc-null Mice Show Increased Microgliosis and Enhanced Funmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia

et al. 2013

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Pectic Galactan Polysaccharide‐Based Gene Delivery System for Targeting Neuroinflammation

Buaron

Mangraviti

Volpin

et al. 2021

Adv Funct Materials

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Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.

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Nano‐Plumber Reshapes Glymphatic‐Lymphatic System to Sustain Microenvironment Homeostasis and Improve Long‐Term Prognosis after Traumatic Brain Injury

Tong,

Xie,

Xie

et al. 2023

Advanced Science

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Long‐term changes in the microenvironment of the brain contribute to the degeneration of neurological function following TBI. However, current research focuses primarily on short‐term modulation during the early phases of TBI, not on the critical significance of long‐term homeostasis in the brain microenvironment. Notably, dysfunction of the glymphatic‐lymphatic system results in the accumulation of danger/damage‐associated molecular patterns (DAMPs) in the brain, which is regarded as the leading cause of long‐term microenvironmental disturbances following TBI. Here, a nanostructure, Nano‐plumber, that co‐encapsulates the microenvironment regulator pro‐DHA and the lymphatic‐specific growth factor VEGF‐C is developed, allowing for a sustainable and orderly regulation of the microenvironment to promote long‐term neurological recovery. Nano‐plumber reverses the injury microenvironment by suppressing microglia and astrocytes activation and maintaining reduced activation via enhanced glymphatic‐lymphatic drainage, and significantly improves the neurological function of rodents with TBI. This study demonstrates that glymphatic‐lymphatic system reconstruction is essential for enhancing long‐term prognosis following TBI, and that the Nano‐plumber developed here may serve as a clinically translatable treatment option for TBI.

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Galectin-3 is upregulated in microglial cells in response to ischemic brain lesions, but not to facial nerve axotomy

Cited by 84 publications

References 32 publications

SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia

SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia

Pectic Galactan Polysaccharide‐Based Gene Delivery System for Targeting Neuroinflammation

Nano‐Plumber Reshapes Glymphatic‐Lymphatic System to Sustain Microenvironment Homeostasis and Improve Long‐Term Prognosis after Traumatic Brain Injury

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