“…14 In adults, the volume of the CSF is 250-450 mL. [13][14][15] The volume of cranial CSF increases between early childhood and middle adulthood, and is larger in the elderly than in younger people. 16 The pH values of the ISF and the CSF are ~7.3 and 7.3-7.4, respectively.…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
confidence: 99%
“…16 The pH values of the ISF and the CSF are ~7.3 and 7.3-7.4, respectively. [13][14][15]17 The CSF is formed by the choroid plexuses of the lateral, third, and fourth ventricles, and by extrachoroidal sources, including the brain parenchyma. Approximately half a liter of CSF is produced per day in humans.…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
confidence: 99%
“…18 The bulk flow of fluid occurs from the lateral to the third and fourth ventricles, before reaching the subarachnoid space (SAS; the space between the arachnoid and pia mater). 19,20 When [ 111 In]diethylenetriamine pentaacetic acid was administered to the lateral ventricles of patients with leptomeningeal metastases, it appeared in the cisterna magna/basal, cervical, thoracic, lumbar SAS, and Sylvian cisterns after 5, 15, 20, 30, and 50 min, respectively (5,8,15,35, and 80 min in children). 21 The CSF leaves the SAS through arachnoid granulations that lead to venous sinuses or along the olfactory nerves into the nasal lymphatics.…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
confidence: 99%
“…19,20 Whereas net CSF flow is directional, second-to-second pulsatile movements allow mixing of its content between the various compartments, especially during non-rapid eye movement sleep. 15 The rate of CSF turnover is still a matter of debate, but has been estimated at 3-4 times each day. 13 Effective delivery of therapeutics from the CSF to the brain parenchyma depends on the blood-CSF barrier (BCSFB), the CSF-brain barrier, and the BBB (Figure 1).…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
Approximately 30% of patients with epilepsy do not respond to pharmacological treatment. In these patients, epilepsy is associated with poor quality of life and an increased risk of morbidity and mortality. 1 Drug resistance has been attributed to pathological processes that can affect both pharmacokinetics and pharmacodynamics (e.g., inflammation). 2 Among the pharmacokinetic contributors is reduced drug distribution to epileptogenic brain tissue across the blood-brain barrier (BBB), 3 which has been associated with locally altered expression of drug transporters and
“…14 In adults, the volume of the CSF is 250-450 mL. [13][14][15] The volume of cranial CSF increases between early childhood and middle adulthood, and is larger in the elderly than in younger people. 16 The pH values of the ISF and the CSF are ~7.3 and 7.3-7.4, respectively.…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
confidence: 99%
“…16 The pH values of the ISF and the CSF are ~7.3 and 7.3-7.4, respectively. [13][14][15]17 The CSF is formed by the choroid plexuses of the lateral, third, and fourth ventricles, and by extrachoroidal sources, including the brain parenchyma. Approximately half a liter of CSF is produced per day in humans.…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
confidence: 99%
“…18 The bulk flow of fluid occurs from the lateral to the third and fourth ventricles, before reaching the subarachnoid space (SAS; the space between the arachnoid and pia mater). 19,20 When [ 111 In]diethylenetriamine pentaacetic acid was administered to the lateral ventricles of patients with leptomeningeal metastases, it appeared in the cisterna magna/basal, cervical, thoracic, lumbar SAS, and Sylvian cisterns after 5, 15, 20, 30, and 50 min, respectively (5,8,15,35, and 80 min in children). 21 The CSF leaves the SAS through arachnoid granulations that lead to venous sinuses or along the olfactory nerves into the nasal lymphatics.…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
confidence: 99%
“…19,20 Whereas net CSF flow is directional, second-to-second pulsatile movements allow mixing of its content between the various compartments, especially during non-rapid eye movement sleep. 15 The rate of CSF turnover is still a matter of debate, but has been estimated at 3-4 times each day. 13 Effective delivery of therapeutics from the CSF to the brain parenchyma depends on the blood-CSF barrier (BCSFB), the CSF-brain barrier, and the BBB (Figure 1).…”
Section: Cerebrospinal Fluid As a Site Of Drug Deliverymentioning
Approximately 30% of patients with epilepsy do not respond to pharmacological treatment. In these patients, epilepsy is associated with poor quality of life and an increased risk of morbidity and mortality. 1 Drug resistance has been attributed to pathological processes that can affect both pharmacokinetics and pharmacodynamics (e.g., inflammation). 2 Among the pharmacokinetic contributors is reduced drug distribution to epileptogenic brain tissue across the blood-brain barrier (BBB), 3 which has been associated with locally altered expression of drug transporters and
“…These blood vessels are fenestrated (60-80 nm openings) and leaky, making them distinct from cerebral penetrating blood vessels which are connected by tight junctions (comprised of occludins, claudins and adhesion molecules) and form the blood-brain barrier (BBB) [ 3 , 6 ]. The Blood-CSF barrier is highly restrictive and regulates the passage of select molecules, ions, and cells (via an array of transport, physical and metabolic machineries) between the blood and the central nervous system (CNS) [ 23 , 24 ]. Fig.…”
Section: Neuroanatomy Of the Choroid Plexusmentioning
The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of a dense network of fenestrated capillary loops that help in the synthesis, secretion and circulation of cerebrospinal fluid (CSF). This unique neuroanatomical structure is comprised of arachnoid villi stemming from frond-like surface projections—that protrude into the lumen of the four cerebral ventricles—providing a key source of nutrients to the brain parenchyma in addition to serving as a ‘sink’ for central nervous system metabolic waste. In fact, the functions of the CP are often described as being analogous to those of the liver and kidney. Beyond forming a barrier/interface between the blood and CSF compartments, the CP has been identified as a modulator of leukocyte trafficking, inflammation, cognition, circadian rhythm and the gut brain-axis. In recent years, advances in molecular biology techniques and neuroimaging along with the use of sophisticated animal models have played an integral role in shaping our understanding of how the CP–CSF system changes in relation to the maturation of neural circuits during critical periods of brain development. In this article we provide an ontogenetic perspective of the CP and review the experimental evidence implicating this structure in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.
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