Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin.

Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.     

Intraorbital cerebrospinal fluid outflow and the posterior uveal compartment of the hamster eye

Summary An ultrastructural and tracer study was undertaken to determine normal outflow pathways of cerebrospinal fluid (CSF) at the terminal subarachnoid space (SAS) of the optic nerve. In the morphological studies, the optic nerve dura and arachnoid were found to be continuous with the sclera of the eye beyond the optic nerve SAS. The pia mater is continuous with the inner sciera and the lamina fusca of the eye. Montages and serial sections demonstrated that the distal SAS is divided into numerous tortuous channels to form an arachnoidal trabecular meshwork. Spaces of this meshwork continue into microcanals which bypass the outer arachnoid barrier layers of the optic nerve meninges to reach the sclera and posterior intraorbital connective tissue. Ferritin infused into the cisterna magna entered the optic nerve SAS within 1 min and reached arachnoidal trabecular meshwork channels and the microcanals within 8 min. It then passed into intraorbital connective tissue spaces at the posterior pole of the eye. Ferritin appeared to be blocked by the lamina fusca and a newly discovered posterior compact zone which together prevented its entrance into the choroidal interstitium. These observations suggest that a subarachnoidal-scleral-orbital outflow pathway provides a route for CSF drainage from the optic nerve SAS to intraorbital connective tissue. The previously described posterior uveal compartment in the hamster eye (Kelly et al. 1983) appears to be relatively isolated from this subarachnoidal-scleral-orbital CSF outflow.Parts of this work have been presented at the 1984 meetings of the American Association of Anatomists (Shen 1984).     

Fluid perfusion as a method of cerebrospinal fluid formation rate--critical appraisal

The aim of the study was to evaluate whether or not cerebrospinal fluid formation rate (Vf) calculated according to the equation of Heisey et al., truly show the produced cerebrospinal fluid. For this reason Vf was simulated (40.6 microL/min) by an infusion pump in a plastic cylinder and the evaluation was done by comparing the results obtained between the calculated Vf and the simulated one. In both cases the result should be the same (40.6 micro/min). Other types of experiments were carried out by ventriculocisternal perfusion (92.4 microL/min) on anaesthetized and sacrificed cats. If the equation is correct, the calculated Vf for sacrificed animals should be zero, because there is no Vf in dead animals. The fact that the calculated Vf (46.5 microL/min) in the plastic cylinder was different (p < 0.0001) from the simulated one (40.6 microL/min) and that Vf was calculated even for dead animals (3-5 microL/min) clearly shows the that perfusion method may not be an accurate method for determination of Vf.     

The human cerebrospinal fluid metabolome

With continuing improvements in analytical technology and an increased interest in comprehensive metabolic profiling of biofluids and tissues, there is a growing need to develop comprehensive reference resources for certain clinically important biofluids, such as blood, urine and cerebrospinal fluid (CSF). As part of our effort to systematically characterize the human metabolome we have chosen to characterize CSF as the first biofluid to be intensively scrutinized. In doing so, we combined comprehensive NMR, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) Fourier transform-mass spectrometry (FTMS) methods with computer-aided literature mining to identify and quantify essentially all of the metabolites that can be commonly detected (with today's technology) in the human CSF metabolome. Tables containing the compounds, concentrations, spectra, protocols and links to disease associations that we have found for the human CSF metabolome are freely available at http://www.csfmetabolome.ca.     

Identification of fibroblasts as a major site of albumin catabolism in peripheral tissues

Rat serum albumin has been labeled with dilactitol-125I-tyramine, (125I-DLT) a radioactive tracer which remains entrapped within lysosomes following cellular uptake and degradation of the carrier protein. Similar kinetics of clearance from the rat circulation were observed for albumin labeled conventionally with 125I or 125I-DLT-albumin, both proteins having circulating half-lives of approximately 2.2 days. In contrast, the recovery of whole body radioactivity had half-lives of approximately 2.2 and 5.1 days, respectively, for the two protein preparations, indicating substantial retention of degradation products derived from catabolism of 125I-DLT-albumin. Measurement of total and acid-soluble radioactivity in tissues 2 or 4 days after injection of 125I-DLT-albumin revealed that skin and muscle accounted for the largest fraction (50-60%) of degradation products in the body. Fibroblasts were identified by autoradiography as the major cell type containing radioactive degradation products in skin and muscle. Fibroblasts were isolated from skin by collagenase digestion, followed by density gradient centrifugation. The amount of acid-soluble radioactivity recovered in these cells was in excellent agreement with that predicted based on acid precipitation of solubilized whole skin preparations. These studies demonstrate for the first time that fibroblasts are a major cell type involved in the degradation of albumin in vivo.     

Cystatin C as a potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt-Jakob disease

The definite diagnosis of Creutzfeldt-Jakob disease (CJD), the most common form of human prion diseases, relies upon neuropathological data usually obtained at autopsy. In living patients, the diagnosis, based on suggestive clinical features and EEG abnormalities, can be aided by the detection of altered levels of isoforms of the 14-3-3 protein in the cerebrospinal fluid (CSF). However, the validity of this test has been recently challenged and the search for other, more reliable biomarkers for CJD remains highly desirable. The present study describes the identification of a new potential surrogate marker in the CSF of CJD-affected patients. A preliminary study employing surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) technology highlighted a protein at 13.4 kDa in a small group (n = 8) of CJD-affected patients. Further analysis aimed at identifying this protein using cationic exchange chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed it to be cystatin C. Additional immunoblot assays confirmed that the level of cystatin C was significantly increased (p 相似文献   

The importance of lymphatics in cerebrospinal fluid transport

Despite the fact that the central nervous system parenchyma does not contain lymphatics, extracranial lymphatic vessels play a very important role in volumetric cerebrospinal fluid (CSF) transport. The most important extracranial location at which lymphatics gain access to CSF is in the nasal submucosa after CSF convects through the cribriform plate. At relatively low intracranial pressures (ICPs), the majority of cranial CSF absorption occurs through this pathway. Global CSF transport parameters in the late gestation fetus and adult sheep are very similar, even though significant numbers of arachnoid projections seem to exist only in the adult. Therefore, extracranial lymphatic vessels play an important role in CSF transport before birth and may represent the primary mechanism for CSF absorption in the neonate. Based on these considerations, hydrocephalus may involve reduced CSF transport to, or into extracranial lymphatic absorption sites.     

The cerebrospinal fluid provides a proliferative niche for neural progenitor cells

Cortical development depends on the active integration of cell-autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.     

Beta-amyloid (Abeta) protein in cerebrospinal fluid as a biomarker for Alzheimer's disease

With the arrival of symptomatic treatment (acetylcholine esterase inhibitors) and the promise of drugs that may delay disease progression, development of diagnostic biomarkers for Alzheimer's disease (AD) are important. Beta-Amyloid (Abeta) protein is the main component of senile plaques. A marked reduction in cerebrospinal fluid (CSF)-Abeta42 in AD has been found in numerous studies. Importantly, reduced CSF-Abeta42 is also found very early in the disease process, before the onset of clinical symptoms. Recent studies suggest that CSF-Abeta42 have a satisfactory performance when used as a diagnostic marker for AD in clinical routine. This paper reviews CSF-Abeta42 as a biomarker for AD.