The dura mater surrounds the arachnoid mater and supports thedural sinuses, which carry blood from the brain to the heart.[8] The area between the arachnoid and pia mater is known as the subarachnoid space. It containscerebrospinal fluid. The arachnoid and pia maters produceprostaglandin D2 synthase, a major cerebrospinal fluid protein.[9] The arachnoid mater provides a restrictive permeability barrier between the cerebrospinal fluid in the subarachnoid space and the circulation of blood in the dura.[5] The pia mater is a thin sheet of connective tissue that interfaces with the glial limitans superficialis.[6]
The dura mater (Latin:tough mother),[10][a] is a durable, thick fibrous membrane that attaches to the inside of theskull and covers the brain and vertebrae. Its dense fibrous tissue is formed from an interlay of collagen fibers, elastin, and fibroblasts in an unformed extracellular matrix.[11] The dura mater is itself a two layered membrane: an outerendosteal (periosteal) layer lies closest to the skull, and an inner (meningeal or dura mater proper) layer lies closer to the brain.[12][6] These layers separate to surround the dural venous sinuses. Sensory and autonomic nerves innervate the dura, and are dense near its blood vessels.[6] The dura's inner surface is covered by flattened fibrocytes which are adhered to by the outer cells of the arachnoid mater.[13] The dura mater surrounds the arachnoid mater and supports thedural sinuses which carry blood from the brain to the heart.[8]
The dura mater folds inwards upon itself to form four areas of infolding called dural reflections:[14][15]
Diagram of section of top of brain showing the meninges and subarachnoid space
Thearachnoid mater, or arachnoid membrane, is the middle element of the meninges. Thin and transparent, its name reflects its resemblance to aspider web. Its fibrous tissue cushions thecentral nervous system. Like the pia mater, it has an outer layer of tightly packed flat cells, forming the arachnoid barrier.[18]
The arachnoid is loosely fitting and does not closely follow theridgesand grooves on the surface of the brain. A large number of fine filaments calledarachnoid trabeculae pass from the arachnoid through the subarachnoid space to blend with the tissue of the pia mater.[19] The arachnoid barrier creates a restrictive permeability barrier between the cerebrospinal fluid in the subarachnoid space and the blood circulation in the dura.[5]
The arachnoid barrier layer is characterized by a distinct continuous basal lamina on its inner surface toward the innermost collagenous portion of the arachnoid reticular layer.[20]
The pia mater (Latin:tender mother)[21] is a very delicate membrane. It is the meningeal envelope that firmly adheres to the surfaces of the brain and spinal cord,[6] following all of the brain's contours (gyri andsulci).[22] It is a very thin sheet of connective tissue that interfaces with the glial limitans superficialis but lacks capillaries itself.[6]
The SLYM would be located in thesubarachnoid space, the space between the middle reticular meninges and the innermost tender meninges that lie close to the brain.[23] It divides the subarachnoid space into an outer, superficial compartment and an inner, deeper area surrounding the brain.[23]
Thearachnoid andpia mater are sometimes together called theleptomeninges,[24] literally "thin meninges" (Greek:λεπτός "leptos"—"thin"). Acutemeningococcal meningitis can lead to anexudate within the leptomeninges along the surface of the brain.[25] Because the arachnoid is connected to the pia by cobweb-like strands, it is structurally continuous with the pia, hence the name pia-arachnoid or leptomeninges. They are responsible for the production of beta-trace protein (prostaglandin D2 synthase), a major cerebrospinal fluid protein.[9]
Diagram of section of spinal cord showing the meninges and spaces. Subarachnoid space coloured blue
Thesubarachnoid space is the space that normally exists between thearachnoid and thepia mater. It is filled withcerebrospinal fluid and continues down thespinal cord. Spaces are formed from openings at different points along the subarachnoid space; theseare thesubarachnoid cisterns, which are filled with cerebrospinal fluid.[26]
The dura mater is attached to theskull,[12] whereas in the spinal cord, the dura mater is separated from thevertebrae by a space called theepidural space, which contains fat and blood vessels. The arachnoid is attached to the dura mater, while the pia mater is attached to the central nervous system tissue. If the dura mater and the arachnoid become separated due to injury or illness, the space between them is known as thesubdural space.[27][28] There is another potential space, thesubpial space, between the pia mater and theglia limitans.[29]
Asubarachnoid hemorrhage is acute bleeding under the arachnoid; it may occur spontaneously or as a result of trauma.[31][30]
Asubdural hematoma (SDH) is an extracerebral collection of blood located in the potential space that can separatearachnoid from the dura mater. The origin is usually venous, caused by injury to thebridging veins that connect the dura mater and thearachnoid. Once these are torn, blood leaks into this area. SDHs occur in about 30% cases of severe head trauma.[30]
Anepidural hematoma (EDH) is a collection of blood between theskull and the dura mater, underlying a bare bone surface. It is often associated with skull fracture. EDH may be arterial (caused by injury of a meningeal artery) or venous (related to damage to of a dural venous sinus or bleeding from diploic veins).[30]
Meningiomas are the most common type of primarybrain tumors to occur in adults. They are thought to arise from meningothelial arachnoid cells in the meninges. Most commonly they attach firmly to the inner surface of the dura and are well-circumscribed; but sometumors may show brain invasion.[32] More rarely,leptomeningeal cancers maymetastasize from tumors elsewhere in the body to the cerebrospinal fluid and leptomeninges.[33]
Migraine is a complex neurovascular pain disorder involving blood vessels, neurons, and cerebrospinal fluid within the meninges. The trigeminal nerve, located within the dura mater, carries sensory information about pain, touch, heat and cold from the face to the brain. The hypothalamus receives input from the trigeminal nerve and can modulate trigeminal nerve activity.[36][37][38] Migraine patients appear to experience impairments incortical habituation, a process which would normally decrease cortical responses to repetitive sensory stimuli.[39][40]
Initiation of a migraine attack may begin with disruption in the hypothalamus and limbic system.[36][37][38] Gradually increasing hypothalamic activity has been observed in the period leading up to a migraine attack, followed by a disruption or collapse of hypothalamic connectivity to the limbic system during an attack.[41] Disruption of the connection between the hypothalamus and limbic system may increase activity in the pain pathway from the trigeminal nerve to the brain, resulting in a migraine attack.[36][37][38]
The meninges, particularly the dura mater, are rich in pain-sensitive nerve endings. Sensory information travels along trigeminal nerve fibers to cell bodies located within the trigeminal ganglion (TG). Axons of the trigeminal ganglion neurons enter the brainstem and travel to the trigeminal nucleus caudalis (TNC).[42][38][5]
The activity ofcalcitonin gene-related peptide (CGRP) in the meninges is linked to migraine.[6] CGRP is released from both the trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) in response to trigeminal nerve activation. CGRP activates receptors on meningeal blood vessels, causing dilation and changes in blood flow. CGRP also activates specialized nerve endings on the dura mater (nociceptors) that transmit pain signals from the dura to the central nervous system. Increased neuronal activity in the trigeminal pain pathway reaches higher cortical pain regions via the brainstem, midbrain and thalamus.[36][38]
Stimulation of the trigeminal nerve may result in release ofneuropeptides such as CGRP,vasodilation of cerebral and dural blood vessels,neurogenic inflammation, and the transmission ofpain signals via nerves in the meninges.[6]Cerebrospinal fluid may also play a role in migraine by transferring signals released from the brain to overlying pain-sensitive meningeal tissues, including dura mater.[6]
Infish, there is a single membrane known as the primitive meninx.[43]Amphibians andreptiles have two meninges, andbirds and mammals have three.[43]Mammals (as higher vertebrates) retain the dura mater, and the secondary meninx divides into thearachnoid andpia mater.[44]
The first known reference to the dura appears in Egypt, in Case 6 of theEdwin Smith Papyrus.Hippocrates described the dura in his monograph "On Injuries of the Head" and insisted that care should be taken to keep it intact and clean.[45]Celsus agreed, and described a method of treatment for depressed fractures.[46]Galen was the first to describe the pia mater in humans in the second century AD.[47]
The arachnoid layer was first described by Dutch physicianGerardus Blasius in 1664.[47]In 1695,Humphrey Ridley first described the subarachnoid cisterns. He also contributed to the understanding of the blood-brain barrier, and accurately described the fifth cranial nerve ganglion with its branches.[48] In 1699,Frederick Ruysch confirmed that the arachnoid mater formed a complete layer that surrounded the brain. Its current name is based on his description of its spiderlike morphology.[49] Arachnoid granulations were first described by Italian physicianAntonio Pacchioni who published hisDissertatio Epistolaris de Glandulis Conglobatis Durae Meningis Humanae in 1705.[50]
In seven articles from 1899 to 1902, Italian anatomistGiuseppe Sterzi described comparative studies on the meninges from thelancelet to the human. He showed that the spinal meninges were very simple in adult lower vertebrates and in the early development of more advanced vertebrates.[51]
^Abbott, NJ; Patabendige, AA; Dolman, DE; Yusof, SR; Begley, DJ (January 2010). "Structure and function of the blood-brain barrier".Neurobiology of Disease.37 (1):13–25.doi:10.1016/j.nbd.2009.07.030.PMID19664713.S2CID14753395.
^Kumar, Vinay (2015).Robbins and Cotran Pathologic Mechanisms of Disease (9th ed.). Philadelphia: Elsevier Saunders. p. 1273.OCLC892583347.In acute meningitis, an exudate is evident within the leptomeninges over the surface of the brain (Fig. 28-21).
^Gundamraj, V; Hasbun, R (1 June 2023). "Viral meningitis and encephalitis: an update".Current Opinion in Infectious Diseases.36 (3):177–185.doi:10.1097/QCO.0000000000000922.PMID37093042.
^abcdeEdvinsson, JCA; Viganò, A; Alekseeva, A; Alieva, E; Arruda, R; De Luca, C; D'Ettore, N; Frattale, I; Kurnukhina, M; Macerola, N; Malenkova, E; Maiorova, M; Novikova, A; Řehulka, P; Rapaccini, V; Roshchina, O; Vanderschueren, G; Zvaune, L; Andreou, AP; Haanes, KA; European Headache Federation School of Advanced Studies, (EHF-SAS) (5 June 2020)."The fifth cranial nerve in headaches".The Journal of Headache and Pain.21 (1): 65.doi:10.1186/s10194-020-01134-1.PMC7275328.PMID32503421.
^Arca, KN; Lambru, G; Starling, AJ (1 January 2024). "Neuromodulation in migraine". In Swanson, JW; Matharu, M (eds.).Handbook of Clinical Neurology, Vol. 199 (3rd series) Migraine Management. Elsevier. pp. 179–200.ISBN978-0-12-823357-3.
^Talamonti, G; D'Aliberti, G; Cenzato, M (January 2020). "Aulus Cornelius Celsus and the Head Injuries".World Neurosurgery.133:127–134.doi:10.1016/j.wneu.2019.09.119.PMID31568909.
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