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Ruben Korolev
Ruben Korolev

Dura Dura

"Dura" is an uptempo reggaeton song with a length of three minutes and twenty seconds, and uses 50s progression.[14] Billboard's Marjua Estevez described the lyrics as "a tender-yet-thirsty ode to the girl Daddy's got his eyes on."[1] She wrote about the song as "Daddy Yankee [kicking] it old-school while singing praises to a love jones."[15] Estevez also clarified that the word "dura" (Spanish for "hard") refers to "a way of saying someone looks hot" in the context of the song.[1]

Dura Dura

Internationally, the song topped the charts of Argentina, Bolivia, Chile, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Nicaragua, Panama, Paraguay, Peru, Spain, and Venezuela, and reached the top 10 in Colombia, Costa Rica, Mexico, the Netherlands, and Uruguay. It also achieved moderate success in Austria, Belgium, Canada, France, Germany, Hungary, Italy, Portugal, Slovakia, and Switzerland. It was the most played song in Latin America on the weeks ending on March 4, 2018, and March 11, 2018, with 13,350 and 13,956 spins across the 18 countries and 700 Hispanic radio stations Monitor Latino measure, respectively.[30][31][32]

Tissue within the parasagittal dura having features as specified above (intermediate or high signal at T2-FLAIR (not free CSF) and at T1-BB (not blood)) was visually identified almost exclusively along the middle to posterior segment of the superior sagittal sinus (Fig. 1; Supplementary Movie 2), corresponding well with the levels where cortical veins enter the sinus.

As expected, CSF tracer also enhanced in macroscopically visible arachnoid granulations, bulging into the sagittal sinus in scattered locations (Fig. 3). As can be noted, the signal change differed somewhat within the CSF of the subarachnoid space, arachnoid granulations and parasagittal dura, suggesting some level of molecular motion restriction between these structures. Supplementary Movie 3 presents an animation of an arachnoid granulation bulging from parasagittal dura in the superior sagittal sinus.

This study demonstrates for the first time direct efflux of a CSF tracer to parasagittal dura in humans. The findings render for the parasagittal dura to represent a bridging link for CSF-mediated exchange of molecules between brain tissue and dural lymphatic vessels.

The region with tracer enhancement, as presented here, stretches laterally to a larger extent than what can be anticipated from the previous anatomical descriptions of intradural human arachnoid granulations14,15, which should be highly suggestive for tracer escape to dura outside arachnoid granulations and into the network of intradural channels. To this end, we note that any CSF or molecular escape to arachnoid granulations whatsoever has lately been questioned7, and explained by commonly accepted assumption of the impermeable arachnoid-barrier.

The present findings also stand in contradistinction to a recent CSF tracer study of mice reporting no signs of tracer propagation through outside the arachnoid layer, and concluding that CSF outflow occurred predominately along cranial nerves through skull neuroforamina7. With concern to clearance rate, another rodent study reported very quick exit of tracer from CSF along perineural routes at the skull base19. In our human cohort, tracer was present in CSF at a far longer time span (even after 2 days), and the tail of the remaining tracer bolus at late scans along parasagittal dura (Fig. 1; Supplementary Movie 1) may also indicate a net drift of CSF molecules in this direction, rather than toward the skull base. These obvious discrepancies between observations in mice and humans underline the importance of human translational research.

It has previously been shown that neurotoxic molecules such as amyloid-β and tau are cleared from brain tissue along paravenous pathways (the glymphatic system)20 and speculated that molecules also drain further along cerebral veins along the brain convexities into dural lymphatic vessels4. A MRI study suggested the same based on peak CSF tracer enhancement in brain and cervical lymph nodes occurring at the same time point21. It has, however, been demonstrated in rats that from the total amount of MRI contrast agent injected into the cisterna magna, merely 19% enriched the brain parenchyma, the remainder escaped via other routes22. Although the dose, injection site and species differences may be important for this fraction, the present observations of high association between tracer enhancement in CSF and adjacent parasagittal dura suggest that molecules within the CSF primarily drain directly to lymphatic pathways. The extent to which this molecular flux may contribute to brain parenchyma clearance remains to be investigated. In this context, previous findings showing that impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain, as well as efflux from the interstitial space5, may suggest that impaired lymphatic clearance function may exert its negative effect directly on the accumulation of molecules within the CSF, and thereby further upstream on molecular exit from brain into CSF.

In conclusion, the present study demonstrates in vivo escape of a CSF tracer from the subarachnoid compartment over the arachnoid and into the parasagittal dura along the superior sagittal sinus in humans. The parasagittal dura may thus represent a bridging link for CSF-mediated exchange of molecules between brain tissue and dural lymphatic vessels.

In areas of parasagittal dura with these features, regions of interest (ROIs) were placed in identical locations at all time points and well within the outer perimeter of parasagittal dura at T1-BB images for robust measurement of T1 signal change as a sign of tracer enrichment. In addition, a ROI was placed within adjacent subarachnoid space to assess T1 signal change in CSF. The CSF tracer enrichment was measured as change in T1-BB signal units, and was normalized against the reference (i.e. the vitreous body of the ocular bulb) to correct for any baseline shift of image grayscale between time points (Supplementary Fig. 1). We also visually assessed any presence of tracer enhancement on T1-BB images below selected cranial nerve outlets at the skull base and dichotomized this as yes/no whether such enhancement was found present at any time point, or not, respectively.

3D T1-GRE scans were used for segmentation and co-registration rendering for 3D representations (using 3D Slicer version 4 and SPM 12, both open source software) illustrating the relations between the brain surface and CSF tracer enhancement. T1-GRE was, however, unsuitable for precise ROI-placement in parasagittal dura, since the border against the enhancing CSF compartment became effaced at late scans (Supplementary Fig. 2).

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The meninges refer to the membranous coverings of the brain and spinal cord. There are three layers of meninges, known as the dura mater, arachnoid mater and pia mater.

The dural venous sinuses are located between the two layers of dura mater. They are responsible for the venous drainage of the cranium and empty into the internal jugular veins.

The arachnoid mater is the middle layer of the meninges, lying directly underneath the dura mater. It consists of layers of connective tissue, is avascular, and does not receive any innervation.

Underneath the arachnoid is a space known as the sub-arachnoid space. It contains cerebrospinal fluid, which acts to cushion the brain. Small projections of arachnoid mater into the dura (known as arachnoid granulations) allow CSF to re-enter the circulation via the dural venous sinuses.

[caption id="attachment_8211" align="alignright" width="154"] Fig 4 - Autopsy of a patient with meningitis. The dura mater is being retracted to show a grossly swollen cerebrum with pus accumulation.[/caption]

Your brain and spinal cord are protected and supported by three meningeal layers. These membrane layers are the dura mater, arachnoid mater and pia mater. The layers plus cerebrospinal fluid keep your brain tissue from jostling against your skull, as well as other functions. Trauma to your head, however, can cause bleeding within any of your meninges and/or your brain tissue itself (intracranial hemorrhage). Be sure to see your healthcare professional if you experience a blow to your head from a trauma (like a car accident), sports injury or fall. 041b061a72


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