Extracellular matrix (ECM) is a network of macromolecules which has two forms-perineuronal nets (PNNs) and a diffuse ECM (dECM)-both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility. Two months after oral treatment of rats with 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan (HA) synthesis, we found downregulated staining for PNNs, HA, chondroitin sulfate proteoglycans, and glial fibrillary acidic protein. These changes were enhanced after 4 and 6 months and were reversible after a normal diet. Morphometric analysis further indicated atrophy of astrocytes. Using real-time iontophoretic method dysregulation of ECM resulted in increased ECS volume fraction α in the somatosensory cortex by 35%, from α = 0.20 in control rats to α = 0.27 after the 4-MU diet. Diffusion-weighted magnetic resonance imaging revealed a decrease of mean diffusivity and fractional anisotropy (FA) in the cortex, hippocampus, thalamus, pallidum, and spinal cord. This study shows the increase in ECS volume, a loss of FA, and changes in astrocytes due to modulation of PNNs and dECM that could affect extrasynaptic transmission, cell-to-cell communication, and neural plasticity.

• MeSH
• Astrocytes metabolism   MeSH
• Chondroitin Sulfate Proteoglycans metabolism   MeSH
• Extracellular Matrix * metabolism   MeSH
• Extracellular Space * metabolism   MeSH
• Glial Fibrillary Acidic Protein metabolism   MeSH
• Hymecromone pharmacology   MeSH
• Rats MeSH
• Hyaluronic Acid MeSH
• Brain metabolism   MeSH
• Nerve Net drug effects   diagnostic imaging   MeSH
• Rats, Sprague-Dawley MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Autobiografie Evy Sykové, české neurofyzioložky, lékařky a političky, která obsahuje také rozhovor.; Kniha profesorky MUD. Evy Sykové, DrSc. mapuje osud ženy, která se musela v životě potýkat s mnoha překážkami a přesto, svou mimořádnou houževnatostí a pílí dosáhla toho, že se stala lékařkou, vědkyní, matkou a političkou.

• MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Physicians, Women history   MeSH
• Neurophysiology history   MeSH
• Politics MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Publication type
• Autobiography MeSH
• Interview MeSH
• Geographicals
• Czech Republic MeSH
• Czechoslovakia MeSH

• Conspectus
• Lékařské vědy. Lékařství
• Biografie
• NML Fields
• neurovědy

• About
• Syková, Eva, 1944- Authority

[This corrects the article DOI: 10.3389/fcell.2021.695900.].

• Publication type
• Published Erratum MeSH

Preclinical and clinical studies with various stem cells, their secretomes, and extracellular vesicles (EVs) indicate their use as a promising strategy for the treatment of various diseases and tissue defects, including neurodegenerative diseases such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Autologous and allogenic mesenchymal stem cells (MSCs) are so far the best candidates for use in regenerative medicine. Here we review the effects of the implantation of MSCs (progenitors of mesodermal origin) in animal models of SCI and ALS and in clinical studies. MSCs possess multilineage differentiation potential and are easily expandable in vitro. These cells, obtained from bone marrow (BM), adipose tissue, Wharton jelly, or even other tissues, have immunomodulatory and paracrine potential, releasing a number of cytokines and factors which inhibit the proliferation of T cells, B cells, and natural killer cells and modify dendritic cell activity. They are hypoimmunogenic, migrate toward lesion sites, induce better regeneration, preserve perineuronal nets, and stimulate neural plasticity. There is a wide use of MSC systemic application or MSCs seeded on scaffolds and tissue bridges made from various synthetic and natural biomaterials, including human decellularized extracellular matrix (ECM) or nanofibers. The positive effects of MSC implantation have been recorded in animals with SCI lesions and ALS. Moreover, promising effects of autologous as well as allogenic MSCs for the treatment of SCI and ALS were demonstrated in recent clinical studies.

• Publication type
• Journal Article MeSH
• Review MeSH

• MeSH
• COVID-19 MeSH

• MeSH
• COVID-19 MeSH

• MeSH
• Microscopy history   MeSH
• Nerve Tissue * MeSH
• Nerve Fibers * MeSH
• Neurons MeSH
• Research history   MeSH
• Publication type
• Historical Article MeSH

• About
• Purkyně, Jan Evangelista, 1787-1869 Authority

Četná kardiovaskulární, neurologická, muskuloskeletální a jiná onemocnění dnes neumíme vyléčit. Objev kmenových buněk přinesl zcela nové možnosti léčby těchto onemocnění. Terapie kmenovými buňkami je na rozhraní mezi moderní regenerativní medicínou a tkáňovým inženýrstvím. Naše experimentální data a první klinické studie využívající kmenové buňky ukazují jejich široký potenciál a přinášejí naději pacientům s širokou škálou devastujících onemocnění. V preklinických studiích pracujeme s lidskými kmenovými buňkami získanými nejen od dospělých dárců z kostní dřeně, tukové tkáně a čichového epitelu, ale i s buňkami fetálními a indukovanými pluripotentními buňkami (iPSC). V probíhajících klinických studiích v oblasti neurologie, ortopedie a diabetologie užíváme jak autologní mononukleární buňky kostní dřeně, tak v GMP prostorách expandované mezenchymální buňky (MSC). V současné době z klinických studií vyplývá, že autologní MSC jsou bezpečné a jejich slibný účinek je třeba dále ověřit v klinických studiích.

Today we are still unable to treat many cardiovascular, neurological, musculoskeletal and other diseases. However, stem cells have brought new possibilities for their treatment. Stem cell therapy lies on the boarder between modern regenerative medicine and tissue engineering. Our experimental data and first clinical studies using stem cells have shown their enormous potential and brings hope to patients with a broad range of devastating diseases. In our preclinical studies we work with human stem cells obtained from bone marrow, adipose tissue and olfactory epithelia of adult donors, as well as with human fetal cells and induced pluripotent stem cells (iPSC). Our current clinical studies in the fields of neurology, orthopedics and diabetology use mesenchymal stem cells (MSC). At present we can conclude from the clinical studies that autologous MSC are safe, their effects are promising but should be futher confirmed in clinical studies.

• MeSH
• Cell- and Tissue-Based Therapy * MeSH
• Clinical Trials as Topic MeSH
• Stem Cells * MeSH
• Humans MeSH
• Guided Tissue Regeneration MeSH
• Stem Cell Transplantation MeSH
• Stem Cell Research * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• MeSH
• Academies and Institutes MeSH
• Research Support as Topic * MeSH
• Science MeSH
• Publication type
• Interview MeSH

• MeSH
• Cell- and Tissue-Based Therapy * trends   MeSH
• Models, Animal MeSH
• Nanoparticles therapeutic use   MeSH
• Guided Tissue Regeneration * trends   MeSH
• Tissue Engineering methods   MeSH
• Stem Cell Transplantation methods   MeSH
• Publication type
• Review MeSH