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Category: neuroscience – Page 37

A prospective study of minimally invasive keyhole craniotomy and stereotactic brachytherapy for new brain oligometastases

Mahapatra et al. show how minimally invasive keyhole craniotomy combined with brachytherapy provides strong local control for brain metastases, with no radiation necrosis and improved neurological and cognitive outcomes, highlighting this approach as a promising alternative to WBRT and SRS. JNOO

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Metastatic brain tumors (MBTs) are the most common intracranial tumors, affecting up to 40% of cancer patients. Traditional treatments such as Whole Brain Radiotherapy (WBRT) and Stereotactic Radiosurgery (SRS) have limitations, including neurocognitive decline and potential tumor regrowth. Minimally invasive keyhole craniotomy (MIKC) and Cesium-131 (Cs-131) brachytherapy offer promising alternatives due to their precision and reduced side effects. This prospective study aims to evaluate the safety and efficacy of combining MIKC with Cs-131 brachytherapy in treating newly diagnosed brain oligometastases.

Twenty-one adults with newly diagnosed brain metastases were enrolled from 2019 to 2021. Preoperative T1 MRI with gadolinium was used to calculate the gross tumor volume (GTV). Minimally invasive craniotomies were performed with resection of these tumors, followed by the implantation of Cs-131 seeds. Postoperative imaging was conducted to verify seed placement and resection. Dosimetric values (V100, V200, D90) were calculated. Patients were followed every two months for two years to monitor local progression, functional outcomes, and quality of life. The primary endpoint was freedom from local progression, with secondary endpoints including overall survival, functional outcomes, quality of life, and treatment-related complications.

The median preoperative tumor volume was 10.65 cm3, reducing to a resection cavity volume of 6.05 cm3 post-operatively. Dosimetric analysis showed a median V100 coverage of 93.2%, V200 of 43.9%, and D90 of 89.8 Gy. The 1-year local freedom from progression (FFP) was 91.67%, while the distant FFP was 53.91%. Five patients remained alive at the study’s end, with a median survival duration of 5.9 months, a duration likely impacted by the concurrent COVID-19 pandemic. Only one patient experienced local recurrence, and no cases of radiation necrosis were observed. Significant improvements were seen in neurological, functional, and cognitive symptoms.

Molecular basis for de novo thymus regeneration in a vertebrate, the axolotl

In humans, the loss of thymic function through thymectomy, environmental challenges, or age-dependent involution is associated with increased mortality, inflammaging, and higher risk of cancer and autoimmune disease (1). This is largely due to a decline in the intrathymic naïve T cell pool, whose generation is orchestrated by the thymic stroma, particularly thymic epithelial cells (TECs) (2). Upon challenges that affect the TEC compartment, the thymus is capable of triggering an endogenous regenerative response by engaging resident epithelial progenitors with stem cell features (3–5). Yet, after age-related atrophy or thymectomy resulting from myasthenia gravis or tumor removal (1), this regenerative response is unable to overcome the loss of thymic tissue, highlighting the need for therapeutic interventions.

The restoration of thymic functionality has been achieved to a limited extent via strategies targeting the thymic epithelial microenvironment or hematopoietic progenitors, modulating hormones and metabolism, or through cellular therapies and bioengineering (6). In mice, the up-regulation of Foxn1, a key transcription factor for thymus development and organogenesis (7), either directly or via its upstream effector bone morphogenetic protein 4 (BMP4), can support activity of cortical TECs (cTECs) (8, 9). Further, a combination of growth hormone and metformin has been shown to restore thymic functional mass in humans (10). Nevertheless, such strategies only lead to delayed thymic involution, and examples of complete thymus regeneration have not yet been described among vertebrates.

Because of its remarkable regenerative abilities that extend to parts of the brain, eye, heart, and spinal cord, and even entire limbs, the axolotl (Ambystoma mexicanum) is a powerful model for regeneration studies (11). The axolotl has offered insights into the mechanisms of positional identity (12), cell plasticity (13, 14), and the molecular basis of complex regeneration (15–18). The regeneration of axolotl body parts relies on remnants of the missing structure, with the exception of lens tissue, which can regrow from dorsal pigmented epithelial cells during a short window during development (19). However, whether de novo regeneration can occur for an entire complex organ, in axolotls or any other vertebrate, is unknown.

Scientists Gave Human Brain Cells to a Rat. Why?

Scientists transplanted human cerebral organoids (“minibrains”) into rats, to better study brain disorders. The neurons grown in vivo looked more like mature human brain cells than those grown in vitro, and they made better models of Timothy syndrome. The human minibrains formed deep connections with the rat brains, received sensory information, and drove the rat’s behavior. Points of Clarification (Q&A based on common comments) Support the channel: / ihmcurious More on how minibrains are grown and used, and the issue of organoid consciousness: • Growing “Mini-Brains” in a Lab: Human Brai… On the topic of organoid sentience and playing pong: • Lab-Grown “Mini-Brain” Learns Pong — Is Th… Organoid transplant study: https://www.nature.com/articles/s4158… music by John Bartmann: https://johnbartmann.com

Cell-Based Neurodegenerative Disease Modeling

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for ALS is currently available. In recent years, cellular therapy has shown considerable therapeutic potential because it exerts immunomodulatory effects and protects the MN circuit. However, the safety and efficacy of cellular therapy in ALS are still under debate. In this review, we summarize the current progress in cellular therapy for ALS. The underlying mechanism, current clinical trials, and the pros and cons of cellular therapy using different types of cell are discussed. In addition, clinical studies of mesenchymal stem cells (MSCs) in ALS are highlighted. The summarized findings of this review can facilitate the future clinical application of precision medicine using cellular therapy in ALS.

ALS is believed to result from a combination of genetic and environmental factors (Masrori and Van Damme 2020). ALS exists in two forms: familial ALS (fALS) and sporadic ALS (sALS). fALS exhibits a Mendelian pattern of inheritance and accounts for 5–10% of all cases. The remaining 90–95% of cases that do not have an apparent genetic link are classified as sALS (Kiernan et al., 2011). At the genetic level, more than 20 genes have been identified. Among them, chromosome 9 open reading frame 72 (C9ORF72), fused in sarcoma (FUS), TAR DNA binding protein (TARDBP), and superoxide dismutase 1 (SOD1) genes have been identified as the most common causative genes (Riancho et al., 2019). Beyond genetic factors, the diverse pathological mechanisms of ALS-associated neurodegeneration have been discussed (van Es et al., 2017). The clinical symptoms of ALS are heterogeneous, with main symptoms including limb weakness, muscle atrophy, and fasciculations involving both upper and lower MNs.

3D maps reveal hidden microenvironments shaping mouse brain connectivity

Recent technological and scientific advances have opened new possibilities for neuroscience research, which is in turn leading to interesting new discoveries. Over the past few years, many groups of neuroscientists worldwide have been trying to map the structure of the brain and its underlying regions with increasing precision, while also probing their involvement in specific mental functions.

As mapping the human brain in detail is often challenging and requires significant resources, many studies focus on other mammals, particularly mice or other rodents. Most mouse brain atlases delineated to date map the density of neurons or other brain cells (i.e., how many cells are packed in specific parts of the brain). In contrast, fewer works also tried to map the shape of neurons in the mouse brain and interactions between them.

Researchers at Fudan University and Southeast University recently set out to map dendrites (i.e., branch-like extensions of neurons via which they receive signals from other cells) in the mouse brain. Their paper, published in Nature Neuroscience, unveils groups of structures in the mouse brain that influence how neurons function and connect to other neurons, also known as microenvironments.

How the cerebellum builds its connections with the rest of the brain during early development

For the first time, a team of researchers at the Institute for Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche (UMH), has reconstructed how the cerebellum establishes its connections with the rest of the brain during the earliest stages of life.

The work, published in the journal Proceedings of the National Academy of Sciences, describes in detail the phases during which these neural connections emerge, expand, and are refined, offering the first comprehensive map of the development of cerebellar projections across the mouse brain.

Although the cerebellum has traditionally been associated with motor control, growing evidence shows that it also plays a role in processes such as emotional regulation, social behavior, and other cognitive functions. However, until now, it was not precisely known when it began interacting with other regions of the brain, communication that is fundamental for these cerebellar roles. This gap motivated the work of the group Development, Wiring and Function of Cerebellar Circuits, led by Juan Antonio Moreno Bravo at the IN.

‘Three-hit model’ involving genes and environment describes possible causes of autism

A new University of California San Diego School of Medicine study offers a unified biological model to explain how genetic predispositions and environmental exposures converge to cause autism spectrum disorder (ASD).

The study, published in Mitochondrion, describes a “three-hit” metabolic signaling model that reframes autism as a treatable disorder of cellular communication and energy metabolism. The model also suggests that as many as half of all autism cases might be prevented or reduced with prenatal and early-life interventions.

“Our findings suggest that autism is not the inevitable result of any one gene or exposure, but the outcome of a series of biological interactions, many of which can be modified,” said study author Robert K. Naviaux, M.D., Ph.D., professor of medicine, pediatrics and pathology at UC San Diego School of Medicine.

Body image issues in adolescence are linked to depression in adulthood, twin study finds

Teenagers who are unhappy with their bodies are more likely to develop symptoms of eating disorders and depression in early adulthood, according to a new study led by University College London (UCL) researchers.

The research, believed to be the first of its kind, followed more than 2,000 twins born in England and Wales. It found that higher body dissatisfaction at age 16 predicted greater symptoms of eating disorders and depression well into the twenties, even after taking into account family background and genetics.

Researchers say the findings strengthen evidence that a negative body image is not just a reflection of poor mental health, but that it can also contribute to it.

Stress hormones can alter brain networks and strengthen emotional memories

Stress influences what we learn and remember. The hormone cortisol, which is released during stressful situations, can make emotional memories in particular stronger. But how exactly does cortisol help the brain build emotional memories?

In a new study, Yale researchers investigated just that. Specifically, they wanted to know how cortisol acts separately on brain circuits that track emotion and those that track memory. They found that cortisol not only helped people remember emotional experiences but also enhanced emotional memory by changing the dynamic brain networks associated with both memory and emotion.

“We all experience stress, and my lab is interested in understanding how stress can be helpful,” said corresponding author Elizabeth Goldfarb, an assistant professor of psychiatry at Yale School of Medicine and of psychology in the Faculty of Arts and Sciences.

Breakthrough uses artificial intelligence to identify different brain cells in action

A decades-old challenge in neuroscience has been solved by harnessing artificial intelligence (AI) to identify the electrical signatures of different types of brain cells for the first time, as part of a study in mice led by researchers from UCL.

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