Is Anesthesia Bad for the Brain? Current Knowledge on the Impact of Anesthetics on the Developing Brain

Background: Cerebral small vessel disease (cSVD), a common risk factor for cognitive impairment, involves unspecific arteriopathy characterized by hypertrophy and endothelial dysfunction that alter cerebrovascular function and auto-regulation of cerebral blood flow (CBF). Microbleedings, subcortical lacunar infarctions and diffuse areas of white matter lesions resulting from vascular injury are associated with reduced cognitive function mostly characterized by difficulties in learning and retention, attention deficits, gait disorders or depression. In recent years, it has become evident that vascular risk factors contribute to the development of cSVD and associated vascular cognitive impairment (VCI). Among them, hypertension emerged as such a major modifiable risk factor since the brain presents an early target for organ damage due to changes in blood pressure (BP). Subsequently both high and, especially in the elderly, low BP have been linked to cognitive decline, which initiated controversial discussions about BP control as a potential therapeutic strategy to achieve optimal brain perfusion and thus, reduce the occurrence of cSVD and cognitive dysfunction. Yet, recent randomized controlled trials examined the impact of anti-hypertensive therapy on cognitive performance with conflicting results. Summary: In light of the current knowledge, it becomes apparent that there is an urgent need to understand the mechanisms underlying hypertension-induced cerebrovascular complications in order to identify effective therapeutic targets to prevent and most importantly also reverse cognitive decline mediated through hypertension. Key Message: This review summarizes the current knowledge of cSVD pathogenesis as well as possible links to hypertension-mediated cerebrovascular complications. By pointing out knowledge gaps, it aims to spur future studies in search of specific targets helping to prevent therapy failures and decelerate the rapidly progressing neuro-degeneration of patients suffering from cerebrovascular diseases emanating from hypertension.

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Nanoplastic Impact on the Gut-Brain Axis: Current Knowledge and Future Directions

International Journal of Molecular Sciences ◽

10.3390/ijms222312795 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12795

Author(s):

Wojciech Grodzicki ◽

Katarzyna Dziendzikowska ◽

Joanna Gromadzka-Ostrowska ◽

Marcin Kruszewski

Keyword(s):

Current Knowledge ◽

Intestinal Barrier ◽

Plastic Pollution ◽

Behavioral Disturbances ◽

Future Directions ◽

Human Environment ◽

Synthetic Materials ◽

Significant Burden ◽

The Impact ◽

The Brain

The widespread usage of plastic places a significant burden on the environment and impacts numerous aquatic and terrestrial species. Humans in particular can be affected by plastic pollution, predominantly via inhalation and ingestion, as well as trophic transfer along the food chain. Under natural conditions synthetic materials undergo degradation into micro- and nanoparticles, especially prone to interact with biological systems. Organisms exposed to nanoplastic accumulate it in multiple tissues, including the gut and the brain. This phenomenon raises a question about the impact of nanoparticulate plastics on the communication pathways between these organs. The aim of this review is to explore an unsettling possibility of the influence of nanoplastic on the gut-brain axis and provide a comprehensive summary of available data regarding this subject. The scarce but consistent evidence shows that exposure to plastic nanoparticles can indeed affect both the digestive and the nervous system. Reported outcomes include microbiota alterations, intestinal barrier permeability, oxidative stress, inflammation, neurotoxicity and behavioral disturbances. Taking into consideration these alarming observations and the ubiquitous presence of plastics in human environment, more research is urgently needed in order to identify any potential threats that nanoplastic exposure can pose to the functioning of the gut-brain axis.

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Physical Activity vs. Redox Balance in the Brain: Brain Health, Aging and Diseases

Antioxidants ◽

10.3390/antiox11010095 ◽

2021 ◽

Vol 11 (1) ◽

pp. 95

Author(s):

Paweł Sutkowy ◽

Alina Woźniak ◽

Celestyna Mila-Kierzenkowska ◽

Karolina Szewczyk-Golec ◽

Roland Wesołowski ◽

...

Keyword(s):

Physical Activity ◽

Physical Exercise ◽

Current Knowledge ◽

Redox Balance ◽

Brain Diseases ◽

Antidepressant Effect ◽

Brain Health ◽

Health Aging ◽

The Impact ◽

The Brain

It has been proven that physical exercise improves cognitive function and memory, has an analgesic and antidepressant effect, and delays the aging of the brain and the development of diseases, including neurodegenerative disorders. There are even attempts to use physical activity in the treatment of mental diseases. The course of most diseases is strictly associated with oxidative stress, which can be prevented or alleviated with regular exercise. It has been proven that physical exercise helps to maintain the oxidant–antioxidant balance. In this review, we present the current knowledge on redox balance in the organism and the consequences of its disruption, while focusing mainly on the brain. Furthermore, we discuss the impact of physical activity on aging and brain diseases, and present current recommendations and directions for further research in this area.

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Effects of Radiation Therapy on Neural Stem Cells

Genes ◽

10.3390/genes10090640 ◽

2019 ◽

Vol 10 (9) ◽

pp. 640 ◽

Cited By ~ 6

Author(s):

Anna Michaelidesová ◽

Jana Konířová ◽

Petr Bartůněk ◽

Martina Zíková

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Side Effects ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Brain Radiotherapy ◽

The Impact ◽

The Brain

Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.

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Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612825666191113103537 ◽

2020 ◽

Vol 25 (42) ◽

pp. 4510-4522 ◽

Cited By ~ 5

Author(s):

Biancamaria Longoni ◽

Irene Fasciani ◽

Shivakumar Kolachalam ◽

Ilaria Pietrantoni ◽

Francesco Marampon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Potential Role ◽

Current Knowledge ◽

Biological Fluids ◽

Cell Communication ◽

Target Cells ◽

Cellular Debris ◽

The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

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Experimental Rodent Models of Vascular Dementia: A Systematic Review

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666210108123438 ◽

2021 ◽

Vol 19 ◽

Author(s):

Nidhi Tiwari ◽

Jyoti Upadhyay ◽

Mohd Nazam Ansari ◽

Syed Shadab Raza ◽

Wasim Ahmad ◽

...

Keyword(s):

Vascular Dementia ◽

Small Vessel Disease ◽

Current Knowledge ◽

Vascular Cognitive Impairment ◽

Experimental Models ◽

New Drugs ◽

Amyloid Angiopathy ◽

Vessel Disease ◽

The Brain ◽

Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

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L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

Genes ◽

10.3390/genes12050682 ◽

2021 ◽

Vol 12 (5) ◽

pp. 682

Author(s):

Matthias Christen ◽

Nils Janzen ◽

Anne Fraser ◽

Adrian C. Sewell ◽

Vidhya Jagannathan ◽

...

Keyword(s):

Current Knowledge ◽

Genetic Defect ◽

Clinical Signs ◽

Missense Variant ◽

Microcytic Anemia ◽

Abnormal Behavior ◽

Functional Candidate Gene ◽

History Of ◽

The Brain ◽

Hydroxyglutaric Acid

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

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The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

Molecular Biology Reports ◽

10.1007/s11033-021-06258-4 ◽

2021 ◽

Vol 48 (3) ◽

pp. 2775-2789

Author(s):

Ludwig Stenz

Keyword(s):

Human Genome ◽

Viral Infections ◽

De Novo ◽

Current Knowledge ◽

Innate Immune ◽

De Novo Mutation ◽

Neuronal Diversity ◽

Alu Sequences ◽

Pol Iii ◽

The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

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Urban Fire Severity and Vegetation Dynamics in Southern California

Remote Sensing ◽

10.3390/rs13010019 ◽

2020 ◽

Vol 13 (1) ◽

pp. 19

Author(s):

Lauren E. H. Mathews ◽

Alicia M. Kinoshita

Keyword(s):

Vegetation Cover ◽

Vegetation Index ◽

Normalized Difference Vegetation Index ◽

Current Knowledge ◽

Fire Severity ◽

Satellite Image ◽

Burn Severity ◽

Native Vegetation ◽

Riparian Areas ◽

The Impact

A combination of satellite image indices and in-field observations was used to investigate the impact of fuel conditions, fire behavior, and vegetation regrowth patterns, altered by invasive riparian vegetation. Satellite image metrics, differenced normalized burn severity (dNBR) and differenced normalized difference vegetation index (dNDVI), were approximated for non-native, riparian, or upland vegetation for traditional timeframes (0-, 1-, and 3-years) after eleven urban fires across a spectrum of invasive vegetation cover. Larger burn severity and loss of green canopy (NDVI) was detected for riparian areas compared to the uplands. The presence of invasive vegetation affected the distribution of burn severity and canopy loss detected within each fire. Fires with native vegetation cover had a higher severity and resulted in larger immediate loss of canopy than fires with substantial amounts of non-native vegetation. The lower burn severity observed 1–3 years after the fires with non-native vegetation suggests a rapid regrowth of non-native grasses, resulting in a smaller measured canopy loss relative to native vegetation immediately after fire. This observed fire pattern favors the life cycle and perpetuation of many opportunistic grasses within urban riparian areas. This research builds upon our current knowledge of wildfire recovery processes and highlights the unique challenges of remotely assessing vegetation biophysical status within urban Mediterranean riverine systems.

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Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽

10.3390/pharmaceutics13060892 ◽

2021 ◽

Vol 13 (6) ◽

pp. 892

Author(s):

Elisa L. J. Moya ◽

Elodie Vandenhaute ◽

Eleonora Rizzi ◽

Marie-Christine Boucau ◽

Johan Hachani ◽

...

Keyword(s):

Drug Discovery ◽

Blood Brain Barrier ◽

Early Stage ◽

Molecular Transport ◽

Brain Barrier ◽

Blood Brain ◽

Cns Drugs ◽

The Impact ◽

The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

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