Radiation-induced neuroinflammation – a potential protective role for PARP (poly ADP ribose polymerase) inhibitors?

Radiotherapy (RT) plays a fundamental role in the treatment of glioblastoma (GBM). GBM are notoriously invasive and harbour a subpopulation of cells with stem-like features which exhibit upregulation of the DNA damage response and are radioresistant. High radiation doses are therefore delivered to large brain volumes and are known to extend survival but also cause delayed toxicity with 50-90% of patients developing neurocognitive dysfunction. Emerging evidence identifies neuroinflammation as a critical mediator of the adverse effects of RT on cognitive function. In addition to its well-established role in promoting repair of radiation induced DNA damage, activation of poly(ADP-ribose) polymerase (PARP) can exacerbate neuroinflammation by promoting secretion of inflammatory mediators. Therefore, PARP represents an intriguing mechanistic link between radiation-induced activation of the DNA damage response and subsequent neuroinflammation. PARP inhibitors have emerged as promising new agents for GBM when given in combination with RT, with multiple preclinical studies demonstrating radiosensitizing effects and at least three compounds being evaluated in clinical trials. We propose that concomitant use of PARP inhibitors could reduce radiation-induced neuroinflammation and reduce the severity of radiation-induced cognitive dysfunction while at the same time improving tumour control by enhancing radiosensitivity.

THE ROLE OF NEURO LINGUISTICS IN CREATIVE WRITING SHORT STORIES THROUGH AN INTERDISCIPLINARY APPROACH

This study aims to explore the role of neurolinguistics in writing creative short stories for students through an interdisciplinary approach. neurolinguistics is a field of study consisting of linguistics and medicine which studies the relationship between language and the human brain which is linked to cognitive neuroscience and sensory and cellular movement. The method used in this research is literature review or literature review. There are four stages or four phases in conducting this research (1) designing a review, (2) conducting a review, (3) analyzing and (4) writing a review. In neurolinguistics, the parts of the human brain are also studied. The brain has 3 main parts, namely the cerebrum (cerebrum), cerebellum (cerebellum), and brainstem (brainstem). There are six factors that must be considered in creative writing, namely general knowledge and cognition, creative cognition, process, motivation and conative, linguistics and literacy, and psychomotor. There are also four-pillar factors of neurolinguistics, namely outcome, rapport, sensory acuity, and flexibility. Neurolinguistics also studies the structure and parts of the human brain, including the cerebrum (large brain), cerebellum (cerebellum), brainstem (brain stem) and limbic system (limbic system). The part that is closely related to writing is the cerebellum (cerebellum).

Experts in action: why we need an embodied social brain hypothesis

The anthropoid primates are known for their intense sociality and large brain size. The idea that these might be causally related has given rise to a large body of work testing the ‘social brain hypothesis'. Here, the emphasis has been placed on the political demands of social life, and the cognitive skills that would enable animals to track the machinations of other minds in metarepresentational ways. It seems to us that this position risks losing touch with the fact that brains primarily evolved to enable the control of action, which in turn leads us to downplay or neglect the importance of the physical body in a material world full of bodies and other objects. As an alternative, we offer a view of primate brain and social evolution that is grounded in the body and action, rather than minds and metarepresentation. This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.

Comparison of embolization strategies for mixed plexiform and fistulous brain arteriovenous malformations: a computational model analysis of theoretical risks of nidus rupture

BackgroundHigh-flow fistulas related to plexiform nidi are found in 40% of large brain arteriovenous malformations (AVMs). Endovascular occlusion of intranidal fistulas before plexiform components is empirically considered safe, but potential ensuing dangerous re-routing of flow through plexiform vessels may in theory raise their rupture risk. It remains unclear whether it is safer to embolize plexiform or fistulous vessels initially. We used a novel biomathematical AVM model to compare theoretical hemodynamic changes and rupture risks on sequential embolizations of both types of nidus vessels.MethodsWe computationally modeled a theoretical AVM as an electrical circuit containing a nidus consisting of a massive stochastic network ensemble comprising 1000 vessels. We sampled and individually simulated 10 000 different nidus morphologies with a fistula angioarchitecturally isolated from its adjacent plexiform nidus. We used network analysis to calculate mean intravascular pressure (Pmean) and flow rate within each nidus vessel; and Monte Carlo analysis to assess overall risks of nidus rupture when simulating sequential occlusions of vessel types in all 10 000 nidi.ResultsWe consistently observed lower nidus rupture risks with initial fistula occlusion in different network morphologies. Intranidal fistula occlusion simultaneously reduced Pmean and flow rate within draining veins.ConclusionsInitial occlusion of AVM fistulas theoretically reduces downstream draining vessel hypertension and lowers the risk of rupture of an adjoining plexiform nidus component. This mitigates the theoretical concern that fistula occlusion may cause dangerous redistribution of hemodynamic forces into plexiform nidus vessels, and supports a clinical strategy favoring AVM fistula occlusion before plexiform nidus embolization.

MET-6 Neoadjuvant fractionated stereotactic radiotherapy followed by piecemeal resection for metastatic brain tumor

BACKGROUND: Large brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative stereotactic radiosurgery (SRS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (Na-SRS) followed by surgery was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation necrosis (RN). We treated with neoadjuvant fractionated stereotactic radiotherapy (Na-fSRT) followed by surgery for large brain metastasis with piecemeal resection. METHODS: Twelve patients received Na-fSRT followed by surgery between July 2019 and April 2021. Na-fSRT dose was based on lesion size and was standard dosing. Surgery generally followed within 7 days after radiotherapy. RESULTS: The mean age was 68 years (51–79). Sixteen men and five women. Mean follow-up period was 8.5 months (1–24.9). Primary were lung; 10 (NSCLC; 9, SCLC (recurrence); 1), esophagus; 3, colon; 2, melanoma; 2, kidney; 2 (recurrence1), uterus body; 1, and liver; 1. The median maximum tumor diameter was 3.6 cm (2.6–4.9). Median PTV, GTV volume were 21.7ml, 15.5ml, respectively. The median fSRT dose was 30Gy/5fr, and the median time from fSRT to surgery was 4 days (1–7). As preoperative adverse event, intracranial hypertension and partial seizure grade 2 (CTCAE ver.5) were occurred, but controlled with steroid and osmotic diuretics and anticonvulsant. Grade 3 and more adverse events were not occurred. Gross total removal was performed in 95.2%. Event cumulative incidence as follows: cavity local recurrence 4.8% (subtotal removal case); distant brain failure 33%; LMD 4.8%; and symptomatic RN 0%. The median intracranial progression free survival was 7 months, and median overall survival was 8.4 months. CONCLUSIONS: Na-fSRT followed by piecemeal resection is safety and feasible, and may have therapeutic value for deep large brain metastasis and eloquent lesion. Further prospective investigations in multi-institutional settings are warranted.

Factors Associated with Cranial Nerve Injury after Radiotherapy for Large Brain Metastases

This paper mainly studied the correlation factors of cranial nerve injury after radiotherapy for large brain metastases by investigating the influencing factors and predictors of cranial nerve injury, which can provide a good reference and idea for radiotherapy. Through a large number of experiments, it is proved that the research idea proposed in this paper is reasonable and correct.

Brain signatures in children who contemplate suicide: learning from the large-scale ABCD study

Background Suicide is the second-leading cause of death in youth. Understanding the neural correlates of suicide ideation (SI) in children is crucial to ongoing efforts to understand and prevent youth suicide. This study characterized key neural networks during rest and emotion task conditions in an epidemiologically informed sample of children who report current, past, or no SI. Methods Data are from the adolescent brain cognitive development study, including 8248 children (ages 9–10; mean age = 119.2 months; 49.2% female) recruited from the community. Resting-state functional connectivity (RSFC) and activation to emotional stimuli in the salience (SN) and default mode (DMN) networks were measured through fMRI. Self-reported SI and clinical profiles were gathered. We examined the replicability of our model results through repeated sub-sample reliability analyses. Results Children with current SI (2.0%), compared to those without any past SI, showed lower DMN RSFC (B = −0.267, p < 0.001) and lower DMN activation in response to negative as compared to neutral faces (B = −0.204, p = 0.010). These results were robust to the effects of MDD, ADHD, and medication use. Sub-sample analysis further supported the robustness of these results. We did not find support for differences in SN RSFC or in SN activation to positive or negative stimuli for children with or without SI. Conclusions Results from a large brain imaging study using robust statistical approaches suggest aberrant DMN functioning in children with current suicide ideation. Findings suggest potential mechanisms that may be targeted in suicide prevention efforts.

Exceptionally Steep Brain-Body Evolutionary Allometry Underlies the Unique Encephalization of Osteoglossiformes

Brain-body static allometry, which is the relationship between brain size and body size within species, is thought to reflect developmental and genetic constraints. Existing evidence suggests that the evolution of large brain size without accompanying changes in body size (that is, encephalization) may occur when this constraint is relaxed. Teleost fish species are generally characterized by having close-fitting brain-body static allometries, leading to strong allometric constraints and small relative brain sizes. However, one order of teleost, Osteoglossiformes, underwent extreme encephalization, and its mechanistic bases are unknown. Here, I used a dataset and phylogeny encompassing 859 teleost species to demonstrate that the encephalization of Osteoglossiformes occurred through an increase in the slope of evolutionary (among-species) brain-body allometry. The slope is virtually isometric (1.03 ± 0.09 SE), making it one of the steepest evolutionary brain-body allometric slopes reported to date, and it deviates significantly from the evolutionary brain-body allometric slopes of other clades of teleost. Examination of the relationship between static allometric parameters (intercepts and slopes) and evolutionary allometry revealed that the dramatic steepening of the evolutionary allometric slope in Osteoglossiformes was a combined result of evolution in the slopes and intercepts of static allometry. These results suggest that the evolution of static allometry, which likely has been driven by evolutionary changes in the rate and timing of brain development, has facilitated the unique encephalization of Osteoglossiformes.