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Computer Methods and Programs in... Mar 2022Accurate finite element (FE) simulation of the optic nerve head (ONH) depends on accurate mechanical properties of the load-bearing tissues. The peripapillary sclera in...
BACKGROUND AND OBJECTIVE
Accurate finite element (FE) simulation of the optic nerve head (ONH) depends on accurate mechanical properties of the load-bearing tissues. The peripapillary sclera in the ONH exhibits a depth-dependent, anisotropic, heterogeneous collagen fiber distribution. This study proposes a novel cable-in-solid modeling approach that mimics heterogeneous anisotropic collagen fiber distribution, validates the approach against published experimental biaxial tensile tests of scleral patches, and demonstrates its effectiveness in a complex model of the posterior human eye and ONH.
METHODS
A computational pipeline was developed that defines control points in the sclera and pia mater, distributes the depth-dependent circumferential, radial, and isotropic cable elements in the sclera and pia in a pattern that mimics collagen fiber orientation, and couples the cable elements and solid matrix using a mesh-free penalty-based cable-in-solid algorithm. A parameter study was performed on a model of a human scleral patch subjected to biaxial deformation, and computational results were matched to published experimental data. The new approach was incorporated into a previously published eye-specific model to test the method; results were then interpreted in relation to the collagen fibers' (cable elements) role in the resultant ONH deformations, stresses, and strains.
RESULTS
Results show that the cable-in-solid approach can mimic the full range of scleral mechanical behavior measured experimentally. Disregarding the collagen fibers/cable elements in the posterior eye model resulted in ∼20-60% greater tensile and shear stresses and strains, and ∼30% larger posterior deformations in the lamina cribrosa and peripapillary sclera.
CONCLUSIONS
The cable-in-solid approach can easily be implemented into commercial FE packages to simulate the heterogeneous and anisotropic mechanical properties of collagenous biological tissues.
Topics: Biomechanical Phenomena; Finite Element Analysis; Humans; Models, Biological; Pia Mater; Sclera
PubMed: 35026624
DOI: 10.1016/j.cmpb.2022.106618 -
Biomolecules Dec 2021Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo...
Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion-reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood-brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (ATR) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion-reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion-reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through ATR or MAS receptors able to affect cerebral microvascular injury.
Topics: Angiotensin I; Angiotensin II; Animals; Benzimidazoles; Biphenyl Compounds; Female; Male; Microcirculation; Microscopy, Fluorescence; Peptide Fragments; Pia Mater; Proto-Oncogene Mas; Rats; Reactive Oxygen Species; Reperfusion Injury; Tetrazoles
PubMed: 34944506
DOI: 10.3390/biom11121861 -
Journal of the American Heart... Jan 2022Background Cerebrovascular autoregulation (CA) regulates cerebral vascular tone to maintain near-constant cerebral blood flow during fluctuations in cerebral perfusion...
Background Cerebrovascular autoregulation (CA) regulates cerebral vascular tone to maintain near-constant cerebral blood flow during fluctuations in cerebral perfusion pressure (CPP). Preclinical and clinical research has challenged the classic triphasic pressure-flow relationship, leaving the normal pressure-flow relationship unclear. Methods and Results We used in vivo imaging of the hemodynamic response in pial arterioles to study CA in a porcine closed cranial window model during nonpharmacological blood pressure manipulation. Red blood cell flux was determined in 52 pial arterioles during 10 hypotension and 10 hypertension experiments to describe the pressure-flow relationship. We found a quadriphasic pressure-flow relationship with 4 distinct physiological phases. Smaller arterioles demonstrated greater vasodilation during low CPP when compared with large arterioles (<0.01), whereas vasoconstrictive capacity during high CPP was not significantly different between arterioles (>0.9). The upper limit of CA was defined by 2 breakpoints. Increases in CPP lead to a point of maximal vasoconstriction of the smallest pial arterioles (upper limit of autoregulation [ULA] 1). Beyond ULA1, only larger arterioles maintain a limited additional vasoconstrictive capacity, extending the buffer for high CPP. Beyond ULA2, vasoconstrictive capacity is exhausted, and all pial arterioles passively dilate. There was substantial intersubject variability, with ranges of 29.2, 47.3, and 50.9 mm Hg for the lower limit, ULA1, and ULA2, respectively. Conclusions We provide new insights into the quadriphasic physiology of CA, differentiating between truly active CA and an extended capacity to buffer increased CPP with progressive failure of CA. In this experimental model, the limits of CA widely varied between subjects.
Topics: Animals; Arterioles; Cerebrovascular Circulation; Homeostasis; Humans; Hypotension; Pia Mater; Swine; Vasodilation
PubMed: 34935426
DOI: 10.1161/JAHA.121.022943 -
Frontiers in Oncology 2021Craniopharyngiomas (CPs) predominantly involving the third ventricle were commonly termed "intraventricular" lesions. The aim of this study was to clarify the anatomical...
Reinvestigating Tumor-Ventricle Relationship of Craniopharyngiomas With Predominantly Ventricular Involvement: An Endoscopic Endonasal Series Based on Histopathological Assessment.
OBJECTIVE
Craniopharyngiomas (CPs) predominantly involving the third ventricle were commonly termed "intraventricular" lesions. The aim of this study was to clarify the anatomical relationship between the tumor and the third ventricle by both surgical and histological investigation.
METHODS
A retrospective review of primarily resected CPs by endoscopic endonasal surgery was performed. CPs with predominantly ventricular involvement were selected for study inclusion by preoperative imaging. The surgical procedure of each case was reviewed. The wholly removed tumor specimens were histologically analyzed, in all cases, to investigate the tumor-third ventricle relationship using hematoxylin and eosin, immunochemical, and immunofluorescence staining.
RESULTS
Twenty-six primary CPs predominantly involving the third ventricle were selected from our series of 223 CPs treated by endoscopic endonasal surgery between January 2017 and March 2021. Gross-total resection was achieved in 24 (92.3%) of 26 patients, with achievement of near-total resection in the remaining patients. A circumferential layer of stretched third ventricle floor was identified surrounding the tumor capsule, which could be peeled off easily from the ventricle floor remnants at most areas of the plane of tumor attachment. Some portions of the tumor capsule tightly adhered to the third ventricle floor were removed together with the floor. A breach of various size was observed at the third ventricle floor after tumor removal in most cases, the floor remaining intact in only two cases (7.7%). Histological examination on marked portions of tumor capsule showed that the pia mater was frequently detected at most of the tumor-brain interface, except at the antero-frontal border of tumor contacting with the third ventricle floor. At this point, a layer of gliosis with various thickness was observed between the tumor and the neural tissue of the third ventricle floor.
CONCLUSION
CPs with predominantly ventricular involvement should be considered as lesions with an extraventricular, epi-pia topography rather than "intraventricular" or "subpial" topography. Accurate understanding of the relationship between the third ventricle and such tumors would predict the circumferential cleavage plane of dissection, and remind neurosurgeons of performing dissection along the safe surgical plane to achieve total tumoral resection with minimizing hypothalamic damage.
PubMed: 34926255
DOI: 10.3389/fonc.2021.740410 -
Neurologia Medico-chirurgica Feb 2022Abnormal hypertrophic arachnoid membranes are often observed in the brain-meningioma interface during microsurgery. They contain fibrosis and tumor cell clusters;...
Abnormal hypertrophic arachnoid membranes are often observed in the brain-meningioma interface during microsurgery. They contain fibrosis and tumor cell clusters; however, preservation of the membranes does not always cause recurrence from the brain surface, and the optimal treatments in the interface remain unclear. We investigated the incidence of recurrence on the brain surface following extra-arachnoid dissection with an approach emphasizing preservation of the arachnoid membranes in meningiomas of World Health Organization (WHO) Grade I. The features of dissection cleavages in the interface were prospectively recorded at surgery. The patients were followed up with MR imaging regularly. In total, 111 patients were included. The median follow-up time was 97.0 (interquartile range [IQR] 70.0-124.0) months. The cleavages in the interface were classified into three subgroups: the Extra-H group (n = 56) with extra-arachnoid resection and preservation of hypertrophic arachnoid membranes, the Extra-N group (n = 39) with extra-arachnoid resection having normal membranes, and the Subpial resection group (n = 16). Tumors recurred in 13 (11.7%) patients at both the brain and dura mater (n = 1) or at the dura mater alone (n = 12). The median recurrence-free survival (RFS) of all recurrences was significantly related to the Simpson grades (P <0.01). For brain surface recurrence, the median RFS was not related to the subgroups. The Karnofsky Performance Scores (KPSs) significantly improved in the patients except for the Subpial group at 3 months after surgery. This study revealed that hypertrophic arachnoid membranes preserved on the brain surface rarely caused recurrence from the brain in WHO Grade I meningiomas after a long-term follow-up.
Topics: Brain; Child; Follow-Up Studies; Humans; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 34719581
DOI: 10.2176/nmc.oa.2021-0209 -
AJNR. American Journal of Neuroradiology Feb 2022The arachnoid membranes are projections of connective tissue in the subarachnoid space that connect the arachnoid mater to the pia mater. These are underappreciated and... (Review)
Review
The arachnoid membranes are projections of connective tissue in the subarachnoid space that connect the arachnoid mater to the pia mater. These are underappreciated and largely unrecognized by most neuroradiologists despite being found to be increasingly important in the pathogenesis, imaging, and treatment of communicating hydrocephalus. This review aims to provide neuroradiologists with an overview of the history, embryology, histology, anatomy, and normal imaging appearance of these membranes, as well as some examples of their clinical importance.
Topics: Arachnoid; Consciousness; Humans; Pia Mater; Radiology; Subarachnoid Space
PubMed: 34711549
DOI: 10.3174/ajnr.A7309 -
Materials Horizons Oct 2021Surface PEGylation, biological camouflage, shape and stiffness modulation of nanoparticles as well as liver blockade and macrophage depletion have all improved the blood...
Surface PEGylation, biological camouflage, shape and stiffness modulation of nanoparticles as well as liver blockade and macrophage depletion have all improved the blood longevity of nanomedicines. Yet, the mononuclear phagocytic system still recognizes, sequesters, and processes the majority of blood borne particles. Here, the natural fatty acid methyl palmitate is combined with endogenous blood components - albumin - realizing ∼200 nm stable, spherical nanoparticles (MPN) capable of inducing a transient and reversible state of dormancy into macrophages. In primary bone marrow derived monocytes (BMDM), the rate of internalization of 5 different particles, ranging in size from 200 up to 2000 nm, with spherical and discoidal shapes, and made out of lipids and polymers, was almost totally inhibited after an overnight pre-treatment with 0.5 mM MPN. Microscopy analyses revealed that MPN reversibly reduced the extension and branching complexity of the microtubule network in BMDM, thus altering membrane bulging and motility. In immunocompetent mice, a 4 h pre-treatment with MPN was sufficient to redirect 2000 nm rigid particles from the liver to the lungs realizing a lung-to-liver accumulation ratio larger than 2. Also, in mice bearing U87-MG tumor masses, a 4 h pre-treatment with MPN enhanced the therapeutic efficacy of docetaxel-loaded nanoparticles significantly inhibiting tumor growth. The natural liver sequestering function was fully recovered overnight. This data would suggest that MPN pre-treatment could transiently and reversibly inhibit non-specific particle sequestration, thus redirecting nanomedicines towards their specific target tissue while boosting their anti-cancer efficacy and imaging capacity.
Topics: Animals; Macrophages; Mice; Nanomedicine; Nanoparticles; Palmitates
PubMed: 34617542
DOI: 10.1039/d1mh00937k -
The Neuroradiology Journal Aug 2022Pial arteriovenous fistulas (AVFs) are rare neurovascular malformations. They differ from arteriovenous malformations (AVMs) in that they involve single or multiple... (Review)
Review
Pial arteriovenous fistulas (AVFs) are rare neurovascular malformations. They differ from arteriovenous malformations (AVMs) in that they involve single or multiple feeding arteries, draining directly into a dilated cortical vein with no intervening nidus. Pial and dural AVFs differ in blood supply, as the first originate from pial or cortical arteries and the latter from outside the dural leaflets. Unlike dural AVFs, most of the pial AVFs are supratentorial. The vast majority are congenital, manifesting during infancy. Acquired pial AVFs are significantly rarer and occur after vasculopathy, head trauma, brain surgery, or cerebral vein thrombosis. We describe a unique case of an acquired pial AVF in a 50-year-old man secondary to a cortical vein thrombosis manifesting as a focal-onset seizure with secondary generalization. A cerebral digital subtraction angiography revealed a low-flow pial AVF fed by a postcentral branch of the left middle cerebral artery draining to the superior sagittal sinus via a cortical vein. It also showed a collateral venous circulation adjacent to the previously thrombosed left parietal vein. There was no evidence of an associated dural AVF or venous varix. Endovascular treatment was scheduled three months later, but the angiogram preceding the embolization showed spontaneous and complete closure of the malformation. To our knowledge, this is the first case illustrating acquired pure pial AVF unaccompanied by a dural component following cortical vein thrombosis, eventually resulting in an unprompted closure.
Topics: Arteriovenous Fistula; Central Nervous System Vascular Malformations; Cerebral Angiography; Cerebral Veins; Humans; Intracranial Thrombosis; Male; Middle Aged; Pia Mater
PubMed: 34609931
DOI: 10.1177/19714009211049080 -
Molecular Pharmaceutics Oct 2021The pharmacokinetic profile of AAV particles following intrathecal delivery has not yet been clearly defined. The present study evaluated the distribution profile of...
The pharmacokinetic profile of AAV particles following intrathecal delivery has not yet been clearly defined. The present study evaluated the distribution profile of adeno-associated virus serotype 5 (AAV5) viral vectors following lumbar intrathecal injection in mice. After a single bolus intrathecal injection, viral DNA concentrations in mouse whole blood, spinal cord, and peripheral tissues were determined using quantitative polymerase chain reaction (qPCR). The kinetics of AAV5 vector in whole blood and the concentration over time in spinal and peripheral tissues were analyzed. Distribution of the AAV5 vector to all levels of the spinal cord, dorsal root ganglia, and into systemic circulation occurred rapidly within 30 min following injection. Vector concentration in whole blood reached a maximum 6 h postinjection with a half-life of approximately 12 h. Area under the curve data revealed the highest concentration of vector distributed to dorsal root ganglia tissue. Immunohistochemical analysis revealed AAV5 particle colocalization with the pia mater at the spinal cord and macrophages in the dorsal root ganglia (DRG) 30 min after injection. These results demonstrate the widespread distribution of AAV5 particles through cerebrospinal fluid and preferential targeting of DRG tissue with possible clearance mechanisms via DRG macrophages.
Topics: Animals; DNA, Viral; Dependovirus; Female; Genetic Vectors; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Real-Time Polymerase Chain Reaction; Spinal Cord; Tissue Distribution; Transduction, Genetic
PubMed: 34460254
DOI: 10.1021/acs.molpharmaceut.1c00252 -
Frontiers in Bioengineering and... 2021Finite Element (FE) modelling of spinal cord response to impact can provide unique insights into the neural tissue response and injury risk potential. Yet, contemporary...
Finite Element (FE) modelling of spinal cord response to impact can provide unique insights into the neural tissue response and injury risk potential. Yet, contemporary human body models (HBMs) used to examine injury risk and prevention across a wide range of impact scenarios often lack detailed integration of the spinal cord and surrounding tissues. The integration of a spinal cord in contemporary HBMs has been limited by the need for a continuum-level model owing to the relatively large element size required to be compatible with HBM, and the requirement for model development based on published material properties and validation using relevant non-linear material data. The goals of this study were to develop and assess non-linear material model parameters for the spinal cord parenchyma and pia mater, and incorporate these models into a continuum-level model of the spinal cord with a mesh size conducive to integration in HBM. First, hyper-viscoelastic material properties based on tissue-level mechanical test data for the spinal cord and hyperelastic material properties for the pia mater were determined. Secondly, the constitutive models were integrated in a spinal cord segment FE model validated against independent experimental data representing transverse compression of the spinal cord-pia mater complex (SCP) under quasi-static indentation and dynamic impact loading. The constitutive model parameters were fit to a quasi-linear viscoelastic model with an Ogden hyperelastic function, and then verified using single element test cases corresponding to the experimental strain rates for the spinal cord (0.32-77.22 s) and pia mater (0.05 s). Validation of the spinal cord model was then performed by re-creating, in an explicit FE code, two independent experimental setups: 1) transverse indentation of a porcine spinal cord-pia mater complex and 2) dynamic transverse impact of a bovine SCP. The indentation model accurately matched the experimental results up to 60% compression of the SCP, while the impact model predicted the loading phase and the maximum deformation (within 7%) of the SCP experimental data. This study quantified the important biomechanical contribution of the pia mater tissue during spinal cord deformation. The validated material models established in this study can be implemented in computational HBM.
PubMed: 34458242
DOI: 10.3389/fbioe.2021.693120