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DNA Damage and Senescence in the Aging and Alzheimer's Disease Cortex Are Not Uniformly Distributed.Biomedicines Jun 2024Alzheimer's disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age dependency of the condition led us to track the...
Alzheimer's disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age dependency of the condition led us to track the appearance of DNA damage in the frontal cortex of individuals who died with a diagnosis of AD. The focus on DNA damage was motivated by evidence that increasing levels of irreparable DNA damage are a major driver of the aging process. The connection between aging and the loss of genomic integrity is compelling because DNA damage has also been identified as a possible cause of cellular senescence. The number of senescent cells has been reported to increase with age, and their senescence-associated secreted products are likely contributing factors to age-related illnesses. We tracked DNA damage with 53BP1 and cellular senescence with p16 immunostaining of human post-mortem brain samples. We found that DNA damage was significantly increased in the BA9 region of the AD cortex compared with the same region in unaffected controls (UCs). In the AD but not UC cases, the density of cells with DNA damage increased with distance from the pia mater up to approximately layer V and then decreased in deeper areas. This pattern of DNA damage was overlaid with the pattern of cellular senescence, which also increased with cortical depth. On a cell-by-cell basis, we found that the intensities of the two markers were tightly linked in the AD but not the UC brain. To test whether DNA damage was a causal factor in the emergence of the senescence program, we used etoposide treatment to damage the DNA of cultured mouse primary neurons. While DNA damage increased after treatment, after 24 h, no change in the expression of senescence-associated markers was observed. Our work suggests that DNA damage and cellular senescence are both increased in the AD brain and increasingly coupled. We propose that in vivo, the relationship between the two age-related processes is more complex than previously thought.
PubMed: 38927534
DOI: 10.3390/biomedicines12061327 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2024The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate... (Review)
Review
The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.
PubMed: 38924700
DOI: 10.1002/ar.25524 -
Experimental and Therapeutic Medicine Jul 2024Sturge-Weber syndrome (SWS) type III, a rare neurocutaneous disorder, presents diagnostic challenges due to its variable clinical manifestations. The present study...
Sturge-Weber syndrome (SWS) type III, a rare neurocutaneous disorder, presents diagnostic challenges due to its variable clinical manifestations. The present study focuses on enhancing the understanding of this syndrome by conducting a detailed analysis of two pediatric cases and providing a comprehensive review of the existing literature. The cases, managed at the Children's Hospital Affiliated to Shandong University (Jinan, China), highlight the diverse clinical presentations and successful management strategies for SWS type III. In the first case, a 4-year-old male patient exhibited paroxysmal hemiplegia, epileptic seizures and cerebral angiographic findings indicative of left pia mater and venous malformation. The second case involved a 2.5-year-old male patient presenting with recurrent seizures and angiographic findings on the right side. Both cases underscore the importance of considering epileptic seizures, acquired and transient hemiplegia and cognitive impairments in the diagnosis of SWS type III. The present study provides insights into the effective use of both pharmacological and surgical interventions, drawing from the positive outcomes observed in these cases. The findings emphasize the need for heightened awareness and a meticulous approach in diagnosing and treating SWS type III, contributing to the better management and prognosis of this condition.
PubMed: 38868613
DOI: 10.3892/etm.2024.12588 -
ACS Applied Materials & Interfaces Jun 2024Exploring the structure-performance relationship of high-voltage organic solar cells (OSCs) is significant for pushing material design and promoting photovoltaic...
Exploring the structure-performance relationship of high-voltage organic solar cells (OSCs) is significant for pushing material design and promoting photovoltaic performance. Herein, we chose a D-π-A type polymer composed of 4,8-bis(thiophene-2-yl)-benzo[1,2-:4,5-']dithiophene (BDT-T) and benzotriazole (BTA) units as the benchmark to investigate the effect of the fluorination number and position of the polymers on the device performance of the high-voltage OSCs, with a benzotriazole-based small molecule (BTA3) as the acceptor. , , and are the polymers with progressively increasing F atoms on the D units, while , , and are the polymers with further attachment of F atoms to the BTA units based on the above three polymers. Fluorination positively affects the molecular planarity, dipole moment, and molecular aggregations. Our results show that increases with the number of fluorine atoms, and fluorination on the D units has a greater effect on than on the A unit. with six fluorine atom substitutions achieves the highest (1.23 V). When four F atoms are located on the D units, the short-circuit current () and fill factor (FF) plummet, and before that, they remain almost constant. The drop in and FF in and based devices may be attributed to inefficient charge transfer and severe charge recombination. The :BTA3 system achieves the highest power conversion efficiency of 9.5% with a of 1.20 V due to the excellent balance between the photovoltaic parameters. Our study provides insights for the future application of fluorination strategies in molecular design for high-voltage organic photovoltaics.
PubMed: 38843444
DOI: 10.1021/acsami.4c05694 -
Heart, Lung & Circulation Jun 2024Safety is of critical importance to chronic total occlusion (CTO) percutaneous coronary intervention (PCI). This global consensus statement provides guidance on how to...
Safety is of critical importance to chronic total occlusion (CTO) percutaneous coronary intervention (PCI). This global consensus statement provides guidance on how to optimise the safety of CTO) PCI, addressing the following 12 areas: 1. Set-up for safe CTO PCI; 2. Guide catheter--associated vessel injuries; 3. Hydraulic dissection, extraplaque haematoma expansion, and aortic dissections; 4. Haemodynamic collapse during CTO PCI; 5. Side branch occlusion; 6. Perforations; 7. Equipment entrapment; 8. Vascular access considerations; 9. Contrast-induced acute kidney injury; 10. Radiation injury; 11 When to stop; and, 12. Proctorship. This statement complements the global CTO crossing algorithm; by advising how to prevent and deal with complications, this statement aims to facilitate clinical practice, research, and education relating to CTO PCI.
PubMed: 38839467
DOI: 10.1016/j.hlc.2023.11.030 -
Progress in Brain Research 2024The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical... (Review)
Review
The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical findings and meningeal damage. Galen proposed that the dura was attached only at the sutures, and he was the first to describe the pia in humans. In the Middle Ages, new interest in the management of meningeal injuries arose, with renewed interest in relating clinical changes to intracranial injuries. These associations were neither consistent nor accurate. The Renaissance brought little change. It was in the 18th century that it became clear that the indication for opening the cranium following trauma was to relieve pressure from hematomas. Moreover, the important clinical findings on which to base an indication for intervention were changes in the level of consciousness.
Topics: Humans; Meninges; History, Ancient; History, 19th Century; History, 18th Century; History, 17th Century; History, Medieval; History, 16th Century; History, 15th Century; History, 20th Century
PubMed: 38705713
DOI: 10.1016/bs.pbr.2024.02.020 -
Neurosurgical Review Apr 2024Pial arteriovenous fistulas (pAVFs) are rare vascular malformations characterized by high-flow arteriovenous shunting involving a cortical arterial supply directly...
BACKGROUND
Pial arteriovenous fistulas (pAVFs) are rare vascular malformations characterized by high-flow arteriovenous shunting involving a cortical arterial supply directly connecting to venous drainage without an intermediate nidus. Dural arteriovenous fistulas (dAVFs) can infrequently involve additional pial feeders which can introduce higher flow shunting and increase the associated treatment risk. In the posterior fossa, arteriovenous fistula (AVF) angioarchitecture tends to be particularly complex, involving either multiple arterial feeders-sometimes from both dural and pial origins-or small caliber vessels that are difficult to catheterize and tend to be intimately involved with functionally critical brainstem or upper cervical cord structures. Given their rarity, published experience on microsurgical or endovascular treatment strategies for posterior fossa pAVFs and dAVFs with pial supply remains limited.
METHODS
Retrospective chart review from 2019-2023 at a high-volume center identified six adult patients with posterior fossa pAVFs that were unable to be fully treated endovascularly and required microsurgical disconnection. These cases are individually presented with a technical emphasis and supported by comprehensive angiographic and intraoperative images.
RESULTS
One vermian (Case 1), three cerebellopontine angle (Cases 2-4) and two craniovertebral junction (Cases 5-6) posterior fossa pAVFs or dAVFs with pial supply are presented. Three cases involved mixed dural and pial arterial supply (Cases 1, 4, and 6), and one case involved a concomitant microAVM (Case 2). Endovascular embolization was attempted in four cases (Cases 1-4): The small caliber and tortuosity of the main arterial feeder prevented catheterization in two cases (Cases 1 and 3). Partial embolization was achieved in Cases 2 and 4. In Cases 5 and 6, involvement of the lateral spinal artery or anterior spinal artery created a prohibitive risk for endovascular embolization, and surgical clip ligation was pursued as primary management. In all cases, microsurgical disconnection resulted in complete fistula obliteration without evidence of recurrence on follow-up imaging (mean follow-up 27.1 months). Two patients experienced persistent post-treatment sensory deficits without significant functional limitation.
CONCLUSIONS
This illustrative case series highlights the technical difficulties and anatomical limitations of endovascular management for posterior fossa pAVFs and dAVFs with pial supply and emphasizes the relative safety and utility of microsurgical disconnection in this context. A combined approach involving partial preoperative embolization-when the angioarchitecture is permissive-can potentially decrease surgical morbidity. Larger studies are warranted to better define the role for multimodal intervention and to assess associated long-term AVF obliteration rates in the setting of pial arterial involvement.
Topics: Humans; Male; Female; Middle Aged; Central Nervous System Vascular Malformations; Aged; Pia Mater; Retrospective Studies; Adult; Arteriovenous Fistula; Cranial Fossa, Posterior; Neurosurgical Procedures; Embolization, Therapeutic; Intracranial Arteriovenous Malformations
PubMed: 38658425
DOI: 10.1007/s10143-024-02407-y -
Cureus Mar 2024Carcinomatous meningitis (CM) is characterized by the multifocal dissemination of malignant cells into the cerebrospinal fluid (CSF), pia mater, and subarachnoid space....
Carcinomatous meningitis (CM) is characterized by the multifocal dissemination of malignant cells into the cerebrospinal fluid (CSF), pia mater, and subarachnoid space. Involvement can occur in the advanced stage of malignancy, causing multifocal involvement and a wide array of symptoms. Diagnosis requires suspicions and a multimodal approach that includes imaging, lumbar puncture, and diagnostic laboratory evaluation. This case represents a female with a history of non-Hodgkin's lymphoma (NHL) and venous thromboembolism on chronic anticoagulation who presented due to acute encephalopathy, hallucinations, and right cranial nerve III palsy for 10 days before arrival. Computed tomography (CT) and angiography of the brain did not show any intracranial abnormalities. Subsequent magnetic resonance imaging (MRI) was without signs of infarction, hemorrhage, or abnormal enhancement, with the MRI of the orbits showing asymmetric linear enhancement anterior to the superior pons and midbrain on the right. Initial differential included a paraneoplastic syndrome, but there was no obvious evidence of pathological enhancement on MRI. Due to progressive bulbar symptoms, a lumbar puncture was performed with cerebrospinal fluid diagnostic workup with cytology showing monoclonal B-cell proliferation consistent with lymphoma. This case illustrates a rare but specific finding of CM as cranial nerve III palsy symptoms in this patient who did not have imaging findings that would reflect her symptoms on the initial MRI of the brain. Furthermore, diagnosing CM is complex and involves a combination of multiple diagnostic and treatment modalities. It is important to recognize the condition early to improve the patient's quality of life, prolong survival, and stabilize neurological deterioration.
PubMed: 38623120
DOI: 10.7759/cureus.56277 -
The American Journal of Pathology Jul 2024Two major constituents of exfoliation material, fibrillin-1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1), are implicated in exfoliation glaucoma, yet their...
Two major constituents of exfoliation material, fibrillin-1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1), are implicated in exfoliation glaucoma, yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of FBN1 mutation and LOXL1 deficiency exacerbates ocular phenotypes, the pan-lysyl oxidase inhibitor β-aminopropionitrile (BAPN) was used to treat adult wild-type (WT) mice and mice heterozygous for a missense mutation in Fbn1 (Fbn1) for 8 weeks and their eyes were examined. Although intraocular pressure did not change and exfoliation material was not detected in the eyes, BAPN treatment worsened optic nerve and axon expansion in Fbn1 mice, an early sign of axonal damage in rodent models of glaucoma. Disruption of elastic fibers was detected only in Fbn1 mice, which increased with BAPN treatment, as shown by histologic and immunohistochemical staining of the optic nerve pia mater. Transmission electron microscopy showed that Fbn1 mice had fewer microfibrils, smaller elastin cores, and a lower density of elastic fibers compared with WT mice in control groups. BAPN treatment led to elastin core expansion in both WT and Fbn1 mice, but an increase in the density of elastic fiber was confined to Fbn1 mice. LOX inhibition had a stronger effect on optic nerve and elastic fiber parameters in the context of Fbn1 mutation, indicating the Marfan mouse model with LOX inhibition warrants further investigation for exfoliation glaucoma pathogenesis.
Topics: Animals; Protein-Lysine 6-Oxidase; Marfan Syndrome; Disease Models, Animal; Mice; Fibrillin-1; Aminopropionitrile; Optic Nerve; Elastic Tissue; Intraocular Pressure; Fibrillins; Mice, Inbred C57BL; Amino Acid Oxidoreductases; Glaucoma; Microfilament Proteins; Adipokines
PubMed: 38548269
DOI: 10.1016/j.ajpath.2024.03.002