Abolished perineuronal nets and altered parvalbumin-immunoreactivity in the nucleus reticularis thalami of wildtype and 3xTg mice after experimental stroke
Abstract
Treatment strategies for ischemic stroke are still limited, since numerous attempts were successful only in preclinical research but failed under clinical condition. To overcome this translational roadblock, clinical relevant stroke models should consider co-morbidities, age-related effects and the complex neurovascular unit (NVU) concept. The NVU includes neurons, vessels and glial cells with astrocytic endfeet in close relation to the extracellular matrix (ECM). However, the role of the ECM after stroke-related tissue damage is poorly understood and mostly neglected for treatment strategies. This study is focused on alterations of perineuronal nets (PNs) as ECM constituents and parvalbumin-containing GABAergic neurons in mice with emphasis on the nucleus reticularis thalami (NRT) in close proximity to the ischemic lesion as induced by a filament-based stroke model. One day after ischemia onset, immunofluorescence-based quantitative analyses revealed drastically declined PNs in the ischemia-affected NRT from 3- and 12-month-old wildtype and co-morbid triple-transgenic (3xTg) mice with Alzheimer-like alterations. Parvalbumin-positive cells decreased numerically in the ischemia-affected NRT, while staining intensity did not differ between the affected and non-affected hemisphere. Additional qualitative analyses demonstrated ischemia-induced loss of PNs and allocated neuropil ECM immunoreactive for aggrecan and neurocan, and impaired immunoreactivity for calbindin, the potassium channel subunit Kv3.1b and the glutamate decarboxylase isoforms GAD65 and GAD67 in the NRT. In conclusion, these data confirm PNs as highly sensitive constituents of the ECM along with impaired neuronal integrity of GABAergic neurons. Therefore, specific targeting of ECM components might appear as a promising strategy for future treatment strategies in stroke.
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PNNs are altered in various neurodevelopmental and neurodegenerative disorders associated with changes in brain activity.
“Recently, increasing evidence suggests that PNNs are altered in various neurodevelopmental and neurodegenerative disorders associated with changes in brain activity (De Luca and Papa, 2016; Sorg et al., 2016; Härtig et al., 2016).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Härtig et al., 2016
In a first set of experiments, significant alterations of ECM constituents-degraded PNs-were shown in the subcortical nucleus reticularis thalami.
“In a first set of experiments that characterized ischemic consequences to the ECM, we were able to show significant alterations of ECM constituents—i.e., degraded perineuronal nets (PNs)—in the subcortical nucleus reticularis thalami (Härtig et al., 2016).”
From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Härtig et al., 2016
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The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
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Self-citationExtracellular matrix modulation is driven by experience-dependent plasticity during stroke recovery.
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- Authors
- Härtig, W., Appel, S., Suttkus, A., Grosche, J., & Michalski, D.
- Affiliations
- Leipzig University (DE)
- University Hospital Leipzig (DE)
- Corresponding author
- Härtig, Wolfgang
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 337
- Pages
- 66-87
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2494951619
- Cited by
- 15
- References
- 19
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 2
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- perineuronal nets, parvalbumin, nucleus reticularis thalami, ischemic stroke, extracellular matrix, neurovascular unit, 3xTg-AD mice, Alzheimer's disease comorbidity, GABAergic neurons, aggrecan, neurocan, calbindin, glutamic acid decarboxylase, stroke treatment strategies
- MeSH terms
- Animals, Disease Models, Animal, Extracellular Matrix, Female, Immunohistochemistry, Male, Mice, Transgenic, Nerve Net, Nerve Tissue Proteins, Neurons, Parvalbumins, Pons, Potassium Channels, Stroke
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