LENTICULOSTRIATE ARTERIOPATHY

LENTICULOSTRIATE ARTERIOPATHY - keywords
lenticulostriate arteriopathy Fetuses of mothers with autoimmune disease (antinuclear, anti-Ro/SSA, anti phospholipid) present with and/or changes in white matter, germinolysis and LSA in up to 36 % (Motta et al. 2011). Depending on the cause, the changes may appear and increase in extent, stabilise and finally regress over weeks. In congenital CMV, hearing deterioration by at least 10dB in at least one ear, seems to be more common in the presence of LSA and this deterioration reached 85 % in untreated infants with arteriopathy as unique sonographic finding (Bilavsky et al. 2015). LSA can also follow postnatal CMV infection (Nijman et al. 2012). For this reason some authors advocate antiviral treatment on the basis of the presence of isolated striatal arteriopathy in CMV-positive neonates. If echoic changes are severe (defined as thick echoic lines extending over at least 2.5 mm, it is suggested to screen for CMV infection (Hong et al. 2015). Late onset arteriopathy has been observed with postnatally acquired CMV infection in VLBW infants (Nijman et al. 2012). LSA has been linked to fetal Zika virus infection (Soares de Souza et al. 2016). In up to 20% of otherwise normal VLBW infants arteriopathy is detected, more often late (beyond the first week) than early in onset, persisting for several months (Robert et al. 2004, Sisman et al. 2015). Infants with late onset of LSA are younger and smaller at birth than infants with early onset. The postmenstrual age, rather than gestational and postnatal age, seems important in LSA development. When encountered in healthy preterm infants, LSA is probably a benign phenomenon: there is currently not enough information to link isolated LSA to behavioural or cognitive outcome in the absence of specific underlying conditions, but further research may be indicated when arteriopathy is extensive (Leijser et al. 2010). histopathology n a v i g a t o r Lenticulostriate vasculopathy (LSV) is the term used for a characteristic hyperechogenicity of the lenticulostriate arteries (Grant et al. 1985). Although thalamic arteries can also be affected, and the name is thus in fact a misnomer, it is in use for long enough to keep it. In some infants the changes are lmited (over a short part of the artery affected) and can be specifically present only in precommissural striatal perforator branches. The term vasculopathy should perhaps be replaced by arteriopathy (hence LSA), because so far only arteries were affected in doppler imaging. In fact the histopathological descriptions of this entity are so scarce that it is not clear whether all such LSAs are indeed an arteropathy or just a change of echoic behaviour of the Virchow-Robin space around a perforator artery. It is likely to be more often a non-specific marker of injury, manifesting after some delay, rather than a specific marker of congenital infection or chromosomal abnormality. This explains why in some cohorts arteriopathy was not associated with CMV infection, for instance (de Jong et al. 2010, Leijser et al. 2010). It also might explain the association between IVH (following matrix haemorrhage) and late onset regional arteriopathy in up to 29 % of the affected compared with 6 % in preterms without IVH (Mittendorf et al. 2004). Any relation with outcome will depend on the associated condition. It is generally accepted that in the absence of TORCH infections, chromosomal abnormalities, associated congenital anomalies, or other underlying conditions, a normal outcome is expected. glymphatics r e f e r e n c e s typical CUS examples differential diagnosis lenticulostriate arteriopathy > imaging lenticulostriate arteriopathy: references Adeeb N, Deep A, Griessenauer CJ, Mortazavi MM, Watanabe K, Loukas M, Tubbs RS, Cohen-Gadol AA (2013) The intracranial arachnoid mater : a comprehensive review of its history, anatomy, imaging, and pathology. Childs Nerv Syst. Jan;29(1):17-33. Alarcón A, Carreras N, Muehlbacher T, Casas-Alba D, Arena R, Roca-Llabrés P, Navarro-Morón J, de Vries LS, Govaert P; EurUS.Brain group. Foetal disruptive brain injuries: Diagnosing the underlying pathogenetic mechanisms with cranial ultrasonography. Dev Med Child Neurol. 2025 Nov;67(11):1383-1408. Ben-Ami T, Yousefzadeh D, Backus M, Reichman B, Kessler A, Hammerman-Rozenberg C. Lenticulostriate vasculopathy in infants with infections of the central nervous system: sonographic and Doppler findings. Pediatr Radiol 1990;20(8):575-579. Bilavsky E, Scharz M, Pardo J, Attias J, Levy I, Haimi-Cohen Y, Amir J. Lenticulostriated vasculopathy is a high risk marker for hearing loss in congenital cytomegalovirus infections. Acta Paediatrica 2015;104: e388-e394. Bode H, Rudin C, Bubl R. Non calcific vasculopathy in the basal ganglia. Klin Padiatr. 1991 Sep-Oct;203(5):350-3. Boulton M, Young A, Hay J, Armstrong D, Flessner M, Schwartz M, Johnston M (1996) Drainage of cerebrospinal fluid through lymphatic pathways and arachnoid villi in sheep: measurement of 125 I- albumin clearance. Neuropathol Appl Neurobiol 22:325-333. Cabañas F, Pellicer A, Morales C, García-Alix A, Stiris TA, Quero J. New pattern of hyperechogenicity in thalamus and basal ganglia studied by color Doppler flow imaging. Pediatr Neurol 1994;10:109–116. Chamnanvanakij S, Rogers CG, Luppino C, Broyles SR, Hickman J, Perlman JM. Linear hyperechogenicity within the basal ganglia and thalamus of preterm infants. Pediatric Neurology. agosto de 2000;23(2):129-33. Chen L, Elias G, Yostos MP, Stimec B, Fasel J, Murphy K (2015) Pathways of cerebrospinal fluid outflow: a deeper understanding of resorption. Neuroradiology 57(2):139-47. Coley BD, Rusin, JA, Boue DR. Importance of hypoxic/ischemic conditions in the development of cerebral lenticulostriate vasculopathy. Pediatr Radiol 2000;30(12):846-855. de Jong EP, Lopriore E, Vossen AC, Steggerda SJ, Te Pas AB, Kroes AC. Is routine TORCH screening warranted in neonates with lenticulostriate vasculopathy? Neonatology 2010;97:274–8. Ding Y, Zhang T, Wu G, McBride DW, Xu N, Klebe DW, Zhang Y, Li Q, Tang J, Zhang JH. Astrogliosis inhibition attenuates hydrocephalus by increasing cerebrospinal fluid reabsorption through the glymphatic system after germinal matrix hemorrhage. Exp Neurol. 2019 Oct;320:113003.El Ayoubi M, de Bethmann O, Monset-Couchard M. Lenticulostriate echogenic vessels: clinical and sonographic study of 70 neonatal cases. Pediatr Radiol 2003;33(10):697-703. Grant EG, Williams AL, Schellinger D, Slovis TL. Intracranial calcification in the infant and neonate: evaluation by sonography and CT. Radiology 1985;157(1):63-8. Gurzu S, Burlacu D, Sánta R, Jung I, Slevin M and Fulop E (2022) Case Report: Coexistence of generalized arterial calcification of infancy (GACI) and maternal infections with cytomegalovirus and Toxoplasma gondii-unexpected fatal complication in a newborn. Front. Pediatr. 10:922379. Hong S-Y, Yang J-J, Li S-Y, Lee I-C. Lenticulostriate vasculopathy in brain ultrasonography is associated with cytomegalovirus infections in newborns. Pediatrics and Neonatology 2015;56:408-414. Jiang Q (2019) MRI and glymphatic system. Stroke and Vascular Neurology 4: e000197. Koral K, Sisman J, Pritchard M, Rosenfeld CR. Lenticulostriate vasculopathy in neonates: perspective of the radiologist. Early Human Development 2015;91:431-435. Kuban KCK, Gilles FH (1985) Human telencephalic angiogenesis. Annals Neurol 1985;17:539–548. Kumar J, Sundaram V, Gupta K, Bhatia A, Kaur G, Dutta S. Congenital Rubella Syndrome as a possible cause for persistent thrombocytopenia in early infancy: The Forgotten Culprit. Autops Case Rep. 2022 Jun 6;12:e2021386. Leijser LM, Steggerda SJ, de Bruine FT, van Zuijlen A, van Steenis A,Walther FJ. Lenticulostriate vasculopathy in very preterm infants. Arch Dis Child Fetal Neonatal Ed 2010;95:F42–6. Makhoul IR, Eisenstein I, Sujov P, Soudack M, Smolkin T, Tamir A, Epelman M. Neonatal lenticulostriate vasculopathy: further characterisation. Arch Dis Child Fetal Neonatal Ed 2003;88 (5):F410-414. Mittendorf R, Covert R, Pryde PG, Lee K-S, Ben-Ami T, Yousefzadeh D. Association between lenticulostriate vasculopathy and neonatal intraventricular hemorrhage. Journal of Perinatology 2004;24: 700-705. Motta M, Zambelloni C, Rodriguez-Perez C, Angeli A, Lojacono A, Tincani A, Chirico G. Cerebral ultrasound abnormalities in infants born to mothers with autoimmune disease. Arch Dis Child Fetal Neonatal Ed 2011;96: F355-F359. Nakada T, Kwee IL (2018) Fluid Dynamics Inside the Brain Barrier: Current Concept of Interstitial Flow, Glymphatic Flow, and Cerebrospinal Fluid Circulation in the Brain. The Neuroscientist 1-12. Nieuwenhuys R, Voogd J, van Huijzenz C (1988) The human central nervous system. Third revised edition. Springer-Verlag. Digital version by Martin Hirsch named ‘Interbrain’. Nijman J, de Vries LS, Koopman-Esseboom C, Uiterwaal CSPM, van Loon A, Verboon-Maciolek MA. Postnatally acquired cytomegalovirus infection in preterm infants: a prospective study on risk factors and cranial ultrasound findings. Arch Dis Child Fetal Neonatal Ed 2012;97: F259-F263. Oreskovic D, Rados M, Klarica M (2017) Role of choroid plexus in cerebrospinal fluid hydrodynamics. Neuroscience 354; 69-87. Pasternak JF, Groothuis DR. Regional variability of blood flow and glucose utilization within the subependymal germinal matrix. Brain Research 1984;299(2):281-8. Raper D, Louveau A, Kipnis J (2016) How Do Meningeal Lymphatic Vessels Drain the CNS ? Trends in Neurosciences, September Vol. 39, No. 9. Robert M, Peter GP, Nancy R. Identification of isolated lenticulostriate vasculopathy in preterm infants. J Perinatol 2004;24:271. Shefer-Kaufman N, Mimouni F, Stavorovsky Z, Meyer JJ, Dollberg S. Incidence and Clinical Significance of Echogenic Vasculature in the Basal Ganglia of Newborns. Amer J Perinatol. 1999;16(06):315-9. Shin HJ, Kim M-J, Lee HS, Namgung R, Park KI, Lee M-J. Imaging patterns of sonographic lenticulostriate vasculopathy and correlation with clinical and neurodevelopmental outcome. J Clin Ultrasound 2015;43: 367-374. Sisman J, Rosenfeld CR. Lenticulostriate vasculopathy in neonates: is it a marker of cerebral insult? Critical review of the literature. Early Human Development 2015;91: 423-426. Sakka L, Coll G, Chazal J (2011) Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol, Head Neck Dis 128:309–316. Soares de Souza A, Moraes Dias C, Braga FD, Tercian AC, Estofolete CF, Oliani AH, Oliveira GH, Brandao de Mattos C, de Mattos LC, Nogueira ML, Vaz-Oliani DC. Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases. Clin Infect Dis 2016; 63(12):1622-1625. Teele RL, Hernanz-Schulman M, Sotrel A. Echogenic vasculature in the basal ganglia of neonates: a sonographic sign of vasculopathy. Radiology 1988;169:423–427. van Baalen A, Rohr A (2009) From fossil to fetus: nonhemorrhagic germinal matrix echodensity caused by mineralizing vasculitis-hypothesis of fossilizing germinolysis and gliosis. J Child Neurol 24 (1): 36-44. Wang HS, Kuo MF, Chang TC. Sonographic lenticulostriate vasculopathy in infants: some associations and a hypothesis. AJNR Am J Neuroradiol 1995;16(1):97-102. < Affected striatal arteries present in CUS as unusual linear echodensities. CUS is the neuroimaging modality of choice to depict LSA. Only densely calcified lesions can be seen on computed tomography, gradient echo or susceptibility-weighted MRI. The changes may show ramification, especially visible in parasagittal sections (candelabra aspect). They almost never produce an acoustic shadow unless densely calcified — proof of which may come from CT scan. Non-calcified lesions will only be seen echographically. True striatal arteriopathy is very often bilateral, but asymmetrical. In parasagittal section a string of dense nodules may show up as transverse sections of thalamostriate arteries just below the outer wall of the lateral ventricle (Makhoul et al. 2003, Koral et al. 2015). Doppler imaging reveals the arterial nature of those densities (Cabanas et al. 1994): inferior striate veins coursing between the perforator arteries are not affected. In many cases the artery can be traced to its origin in the MCA in a less echoic form. Generally the lesions are pulsatile, although flow may be absent or difficult to detect. Flow velocities do not obviously differ from those in normal brains (striatal branches can always be visulaised with colour or power Doppler imaging), although this needs further study. In normal infants one can also see weaker (less bright and slimmer) echoreflections from these vessels. The transition to pathology resides in an increased echogenicity that is difficult to prove objectively, and in the impression that reflections are wider and, in certain places, nodularly thickened when pathological (El Ayoubi 2003). Punctiform foci can be found in or at arteries, and their pathologic nature is dubious; they are often located under the head of the caudate nucleus. We suspect that these are tangentially sectioned Virchow–Robin spaces around a normal artery, but there is no histological confirmation of this. Clearly sharper definitions are needed, also in the context of higher resolution ultrasound probes, including some measure of extent and degree of (peri)vascular echogenicity and perhaps also including alterations in perfusion indices through affected arteries (Shin et al. 2015), all this preferably combined with postmortem findings in some infants. LSV can be graded on CUS as (El Ayoubi et al. 1990, Shin et al. 2015, Koral et al. 2015): - minor (one streak) - moderate (one or two bilateral streaks) - major (three or more bilateral streaks). moderate MRI chronic stage lenticulostriate arteriopathy: imaging major minor typical major arteriopathy in a term infant with meconium aspiration: this is probably an example of non-specific inflammation along perforator arteries and not arteritis postnatal onset (1) leukaemia ZIKA postnatal onset (2) typical antenatal onset trisomy 13 Aicardi-Goutières postnatal onset (3) lenticulostriate arteriopathy: imaging examples Zellweger precommissural generalised arterial calcinosis thalamic Teele et al. 1988: "clinical diagnoses were cytomegalovirus infection (five), rubella (two), congenital syphilis (one), and trisomy 13 syndrome (three); at neuropathologic examination, perforating medium-sized arteries to the basal ganglia and thalami had thickened hypercellular walls, with deposits of amorphous basophilic material in three infants; results of computed tomography and radiography of brain sections were normal in these areas" lenticulostriate arteriopathy: neuropathology The pathological correlate consists of inflammation or mineralization of the perforators, medium-sized arteries supplying the basal ganglia and the thalami (Teele et al. 1988 a newborn with CMV, Cabanas et al. 1995 a newborn with trisomy 18, Wang et al. 1995) and/or hyperechoic changes in the Virchow-Robin space around them. There are however very few pathological descriptions, no doubt also histologically heterogeneous. There may in some infants be a link with multilocular cystic germinolysis (van Baalen et al. 2009). Cranial ultrasound “rediscovered” LSA, an entity that is surprisingly frequent: it is found in routine CUS in 0.4 % of all liveborn neonates, and 1.9-5.8 % of sick or preterm neonates (Wang et al. 1995, Shefer-Kaufman et al. 1999, Chamnanvankij et al. 2000, Makhoul et al. 2003). The recognition with MRI is difficult although the condition often hints to an ongoing problem. Apparently the histological changes and location in deep grey matter are ideal for detection with CUS but not MRI. Affected lenticulostriate arteries are branches of the MCA and Heubner’s artery from the ACA, that perfuse upwards to the scanhead in the anterior fontanelle. These vessels are prominent in fetal life because they perfuse germinal matrix and fast growing striatum and thalamus. In a minority, intrathalamic arteries are also affected, stemming from the circle of Willis and/or the PCA. Why MCA perforators seem preferentially affected is unclear. One of the explanations might be found in the normal dynamics of angiogenesis: in third trimester a muscular coat is formed around striatal arteries, whereas in arteries in white matter this does not happen until term (Kuban and Gilles 1985). Blood flow in the lenticulostriate arteries is high in utero, as there is active proliferation of the germinal matrix in the caudothalamic groove (Pasternak and Groothuis 1984). Minor insults may produce changes in tissue perfused by these high-flow vessels (Wang et al. 1990). Histological changes in the vessel wall have been well documented for entities like CMV, rubella and hypoxia/ischaemia, and findings were summarized as mineralizing vasculopathy with basophilic deposits in the arterial wall (Teele et al 1988, Ben-Ami et al. 1990, Coley et al 2000, Gurzu et al. 2022). Alternative to changes in the wall of the artery is increased cellular quantity of the Virchow-Robin space that surrounds these perforators, which would explain that the limited postmortem studies on the subject have not documented arterial changes in all infants (Teele et al. 1988). It is not uncommon to observe the appearance of striatal arteriopathy with ultrasound, after initial normal serial scans in preterm infants, often (not only) following GMH/IVH. This could be an indicator of deposits along perforator arteries related to glymphatic drainage. As experimental support for this idea, GMH was induced by stereotaxic collagenase infusion into P7 Sprague-Dawley rats of both sexes (Ding et al. 2019). Western blot and immunofluorescence were used to assess astrogliosis and its effect on glymphatic function by measuring Aquaporin-4 expression. Intracisternal injection of fluorescence tracer was used to measure CSF diffusion throughout the brain, its dispersion in the paravascular area and CSF drainage into the deep cervical lymph nodes at 28  days after GMH. Nissl staining was used to assess the morphological changes at 28  days after haemorrhage. GMH elicited astrogliotic scarring and reduced the exchange between CSF and interstitial fluid, as well as CSF reabsorption through the meningeal lymphatic vessels. This was associated with redistribution of Aquaporin-4. This suggested that the glymphatic system might play a role in CSF reabsorption in neonates following GMH. Scar tissue formation impairs this CSF clearance route. If this is confirmed by human study, there could indeed be a relation between germinolysis, LSA and glymphatics. Kumar et al. 2022: amphophilic calcific deposits seen around the brain blood vessels (H&E x400) in congenital rubella syndrome courtesy Fernando Cabanas, Madrid: subendothelial deposits in trisomy 18 along a striatal artery mitochondrial disorder Clinical conditions with hyperechoic perforator arteries------------------------------------------------------------------------ 1. Fetopathy (Grant et al. 1985, Teele et al. 1988, Cabanas et al. 1995, Wang et al. 1995, Bilavsky et al. 2015, Hong et al. 2015, Soares de Souza et al. 2016, de Vries 2019): CMV, rubella virus, HSV, rotavirus, Treponema pallidum, VZV, neonates of HIV+ mothers (not necessarily infected themselves), Zika virus; although typical LSA instances are due to vasculitis from infection, the prevalence of fetopathy as a cause of striatal vasculopathy is in the order of 10%; late onset arteriopathy has been reported in neonatally acquired CMV infection, also in fetopathy look-alikes (see below: pseudo-Torch, Aicardi-Goutières and Boltshauser syndromes, Norrie disease) 2. Asphyxia (≈ 10 %): fetal, perinatal and postnatal 3. Chromosomal anomaly (≈ 10 %): trisomy 21 (precursor to later amyloid vasculopathy ?), trisomy 13, del 5q, unbalanced chro 11 translocation, 46XX/47XXX mosaicism, Miller-Dieker syndrome (Wang et al. 1995, Chabra et al. 1997) 4. Metabolic disorders: (not reported in amino acid and urea cycle disorders) Zellweger syndrome Lowe syndrome pyruvate dehydrogenase deficiency desmolase deficiency glutaric aciduria type II infantile arterial calcinosis storage disorders (neurosialidosis) (Ries et al. 1992) 5. Bacterial meningitis, e.g. GBS 6. Syndromal: leukodystrophy, Weaver syndrome, Sotos syndrome, congenital Finnisch type nephrosis, Smith–Lemli–Opitz syndrome, linear naevus sebaceus, contractural arachnodactyly, eosinophilia-ichtyosis-prematurity, incontinentia pigmenti, multisystemic smooth muscle dysfunction by ACTA 2 mutation; other genetic cerebrovascular disease (see below) 7. Associated with haemorrhage in germinal matrix in preterm infants (Mittendorf et al. 2004) 8. Recipient twin in twin to twin transfusion syndrome or twin anaemia polycthemia sequence; uncommon in dichorionic twins (de Vries et al. 1995, Denbow et al. 1998, El-Ayoubi et al. 2003) 9. Maternal conditions affecting the fetus: heroin abuse, diabetes mellitus, fetal alcohol syndrome (Wang et al. 1995), Kawasaki disease. Neonatal lupus (Cabanas et al. 1994, Motta et al. 2011); also cases of antiphospholipid syndrome, allo-immune thrombocytopenia and maternal ITP 10. Miscellaneous: neonatal hypothyroidism, neonatal leukemia, congenital heart disease (Coley et al. 2000, El-Ayoubi et al. 2003, Mebius et al. 2017), meconium aspiration Genetic vascular disease of antenatal onset (Alarcon et al. 2025)----------------------------------------------------------------------------------- basement membrane disorder: COL4A1/COL4A2 mutations - smooth muscle dysfunction: ACTA2 mutations - connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome - cervical and intracranial arterial anomalies: PHACE syndrome - copper metabolism disorder, vascular tortuosity: Menkes disease - laminin A aberration: LMNA mutations - type I interferonopathies causing inflammatory vasculopathy: Aicardi–Goutières syndrome and others (X-L)(NF-KappaB Essential Modulator) - incontinentia pigmenti: obliteration of small and medium sized arteries in the neonatal period - tight junction dysfunction: JAM3 mutation - CNS haemangioblastoma: Von Hippel-Lindau disease - venous malformation: Sturge-Weber syndrome - neurofobromatosis type 1 and 2: moyamoya arteriopathy, cerebral aneurysms, stenotic, or ectatic cerebral vessels; risk of ischaemic or haemorrhagic complications - arteriovenous malformation: Hereditary Haemorrhagic Telangiectasia, capillary malformation-arteriovenous malformation syndrome - accumulation of globotriaosylceramide (GL-3) within lysosomes in different cell types, including endothelial cells: Fabry disease - metabolic stroke: mitochondrial disorders, acute cellular energy failure: molybdenum cofactor deficiency lenticulostriate arteriopathy: differential diagnosis lenticulostriate arteriopathy: glymphatics CSF is absorbed and drained in bulk not just through cerebral but also spinal arachnoid granulations, and a lymphatic pathway involving egress through cranial (particularly the olfactory nerve) and spinal nerve sheaths. In the spinal subarachnoid space, the remaining CSF which is not absorbed by spinal arachnoid granulations or spinal nerve sheaths circulates rostrally toward the cranial subarachnoid space. Brain interstitial fluid, ependyma and capillaries play a role in CSF secretion in addition to choroid plexus. CSF circulation from sites of secretion to sites of absorption largely depends on the arterial pulse wave. Additional factors such as respiratory waves, posture, jugular venous pressure and physical effort also modulate CSF flow dynamics and pressure. A CSF-interstitium exchange, now termed a ‘glymphatic’ system, has been proposed as a mechanism for the removal of macromolecules from the parenchyma into CSF. This system relies on the influx of CSF into the brain parenchyma possibly through periarterial spaces. Efflux is, along with both hydrophilic and lipophilic compounds, through the paravascular spaces back into the subarachnoid space. The efficiency of the system relies on arteriole pulsatility and CSF pressure, and appears to be dependent (at least partially) on the water channel AQP4. This system appears to be more efficient during sleep. Whether efflux from the brain parenchyma (into CSF) is along periarterial or perivenular spaces remains a matter of debate. The meningeal lymphatic system has emerged as a player in CSF flow. Experimental data suggest that cranial and spinal nerve sheaths, the cribriform plate and the adventitia of cerebral arteries constitute substantial pathways of CSF drainage into the lymphatic outflow system (Raper et al. 2016). CSF is renewed about four times every 24 hours. Reduction of the CSF turnover rate during aging leads to accumulation of catabolites in the brain and CSF that are also observed in certain neurodegenerative diseases. Because of the tight junctions of brain capillary endothelium, the interstitial fluid system of the brain cannot benefit from the hydrodynamic force of the systolic pulse of the heart, and interstitial fluid may become “stagnant” without a proper hydrodynamic alternative. AQP-4 localized to endfeet at the GLE is believed to play the role of ensuring proper water influx into the intracellular space of astrocytes (Nakada et al. 2018). The AQP-4 system provides water influx into the peri-capillary Virchow-Robin space (VRS). Necessary water enters astrocytes through AQP-4 at the glia limitans externa (GLE). This system promotes appropriate interstitial fluid circulation, including bulk flow through the VRS (Virchow-Robin space) (interstitial flow). In order to have a hydrodynamic condition similar to that of the systemic environment with its fenestrated capillaries, water influx has to be provided into the peri-capillary VRS. The astrocyte aquaporin-4 (AQP-4) system effects this by removing water out of the subpial space and infusing water into peri-capillary VRS. The system creates the proper hydrodynamic environment for interstitial circulation as well as glymphatics. ——> Waste clearance during sleep: changes in efficiency of CSF–interstitial fluid exchange between the awake and sleeping brain are caused by expansion and contraction of the extracellular space, which increases by ~60% during sleep to promote clearance of interstitial wastes such as amyloid beta; the restorative properties of sleep may be linked to increased glymphatic clearance of metabolic waste products produced by neural activity in the awake brain. ——> Lipid transport: important role in transporting small lipophilic molecules; paravascular transport of lipids through the glymphatic pathway activates glial calcium signalling; impairment of the glymphatic circulation leads to unselective lipid diffusion, intracellular lipid accumulation and pathological signalling among astrocytes. lenticulostriate arteriopathy: glymphatics and lymphatics Mac OS X 2?qATTRqøyøcom.apple.TextEncodingHcom.apple.maclOcom.apple.provenanceZcom.apple.quarantineutf-8;134217984@â¥�,’E–—/Z‹kñÂ.Im0ÖWq/0082;699affc1;Hype4;

Cerebrus