Hyaluronidase inhibition accelerates functional recovery from stroke in the mouse brain

Greda, A.; Nowicka, Dorota

doi:10.1111/jnc.15279

Cited by 14 publications

(9 citation statements)

References 84 publications

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“…Tang and colleagues have found an inverted U-shaped association between plasma hyaluronan and clinical outcome suggesting lower and higher plasma hyaluronan levels tend to associate with poor clinical outcome [ 48 ]. Interestingly, inhibition of hyaluronidase, the enzyme responsible for the liberation of hyaluronan fragments from the extracellular matrix, has been shown to improve the functional outcomes after ischemic stroke [ 51 ]. Expression of another extracellular matrix DAMP, tenascin C, was found to upregulate after experimental ischemic stroke, and interestingly, the knockout of tenascin C compromised the exploratory and surveillance activity of the microglia and led to the increased infiltration of peripheral leukocytes, particularly T cells [ 52 ].…”

Section: Means Of Interaction Between Brain and Immune Cellsmentioning

confidence: 99%

Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Muhammad

Chaudhry

Kahlert

et al. 2021

Cells

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Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.

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Section: Means Of Interaction Between Brain and Immune Cellsmentioning

confidence: 99%

Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Muhammad

Chaudhry

Kahlert

et al. 2021

Cells

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“…SHR micelles with intact morphology either enter cells via CD44 receptor-mediated endocytosis or enter into cells and target damaged mitochondria through the excellent transmembrane action of SS-31. However, HR micelles, which were generated by partial degradation of HA by Hya-1, 30 can also enter cells via CD44 receptor-mediated endocytosis. Free RT, which was released by SHR or HR micelles, can directly bind to ACE2 receptors on the surface of the cell membrane to exert therapeutic effects on the damaged tissue.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

A Triple-Targeted Rutin-Based Self-Assembled Delivery Vector for Treating Ischemic Stroke by Vascular Normalization and Anti-Inflammation via ACE2/Ang1-7 Signaling

Zhao,

He,

Zhao

et al. 2023

ACS Cent. Sci.

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Changes in the cerebral microenvironment caused by acute ischemic stroke-reperfusion are the main obstacle to the recovery of neurological function and an important cause of stroke recurrence after thrombolytic therapy. The intracerebral microenvironment after ischemia-reperfusion reduces the neuroplasticity of the penumbra and ultimately leads to permanent neurological damage. To overcome this challenge, we developed a triple-targeted self-assembled nanodelivery system, which combines the neuroprotective drug rutin with hyaluronic acid through esterification to form a conjugate, and then connected SS-31, a small peptide that can penetrate the blood brain barrier and target mitochondria. Brain targeting, CD44-mediated endocytosis, hyaluronidase 1-mediated degradation, and the acidic environment synergistically promoted the enrichment of nanoparticles and drug release in the injured area. Results demonstrate that rutin has a high affinity for ACE2 receptors on the cell membrane and can directly activate ACE2/Ang1-7 signaling, maintain neuroinflammation, and promote penumbra angiogenesis and normal neovascularization. Importantly, this delivery system enhanced the overall plasticity of the injured area and significantly reduced neurological damage after stroke. The relevant mechanism was expounded from the aspects of behavior, histology, and molecular cytology. All results suggest that our delivery system may be an effective and safe strategy for the treatment of acute ischemic stroke-reperfusion injury.

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“…HAS1 encodes an enzyme producing hyaluronan and with expression induced by inflammation and glycemic stress 48 . Of note, an increased hyaluronan turnover has been suggested to follow ischemic stroke 49 . HAS1 replication was not feasible in T1D due to absent mutation carriers, thus, a diabetes-specific replication is pending.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome sequencing identifies variants inANK1,LRRN1,HAS1,and other genes and regulatory regions for stroke in type 1 diabetes

Antikainen

Haukka

Kumar

et al. 2022

Preprint

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Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Therefore, we studied stroke genetics in individuals with T1D using whole-genome sequencing (N=571) and whole-exome sequencing (N=480). We attempted replication of the lead discoveries in our T1D specific cohort using a genome-wide association study (N=3,945) and genotyping (N=3,600), and in the general population from the large-scale population-wide FinnGen project and UK Biobank summary statistics. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. We discovered T1D specific stroke loci on 4q33-34.1, SREBF1, and ANK1; and stroke loci that likely generalize to the non-diabetic population on HAS1, LRRN1, UACA, LTB4R, LINC01500 (promoter capture loop to DACT1), and TRPM2-AS promoter. We further validated the promoter with an in vitro cell-based assay.

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Hyaluronidase inhibition accelerates functional recovery from stroke in the mouse brain

Cited by 14 publications

References 84 publications

Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

A Triple-Targeted Rutin-Based Self-Assembled Delivery Vector for Treating Ischemic Stroke by Vascular Normalization and Anti-Inflammation via ACE2/Ang1-7 Signaling

Whole-genome sequencing identifies variants inANK1,LRRN1,HAS1,and other genes and regulatory regions for stroke in type 1 diabetes

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