scispace - formally typeset
Search or ask a question

Showing papers on "Cerebrospinal fluid published in 1996"


Journal ArticleDOI
TL;DR: The results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagonize TNF alpha should be carried out with frequent monitoring of gadolinium-enhanced MRIs.
Abstract: There is evidence that treatment with an antibody to tumor necrosis factor alpha (TNF alpha) improves an animal model of multiple sclerosis (MS) and is beneficial in two systemic inflammatory disease in humans, but there are no reports about anti-TNF treatment of MS. Therefore, we treated two rapidly progressive MS patients with intravenous infusions of a humanized mouse monoclonal anti-TNF antibody (cA2) in an open-label phase I safety trial and monitored their clinical status, gadolinium-enhanced brain magnetic resonance imaging (MRI), and peripheral blood and cerebrospinal fluid (CSF) immunologic status. We did not notice any clinically significant neurologic changes in either patient. The number of gadolinium-enhancing lesions increased transiently after each treatment in both patients. CSF leukocyte counts and IgG index increased after each treatment. The transient increase in the number of gadolinium-enhancing lesions that followed each infusion of cA2 together with the increase in cells and immunoglobulin in the CSF of each patient suggest that the treatment caused immune activation and an increase in disease activity. These results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagonize TNF alpha should be carried out with frequent monitoring of gadolinium-enhanced MRIs.

714 citations


Book
15 Jan 1996
TL;DR: Chemical composition and secretory nature of the fluid the blood-brain barrier the return of CSF to the blood the drainage mechanism the intracranial or CSF pressure.
Abstract: Introduction Chemical Composition and Secretory Nature of the Fluid The Blood-Cerebrospinal Fluid Barrier The Blood-Brain Barrier Morphological Aspects of the Barriers The Secretion of the Cerebrospinal Fluid Blood-Brain-CSF Relations Special Aspects of the Blood-Brain Barrier Acid-Base Relations in the Central Nervous System The Return of the CSF to the Blood: The Drainage Mechanism Breakdown of the Barriers and the Cerebral Oedema The Proteins and Other Macromolecules of the CSF Ortogenetic Aspects of the Cerebrospinal System Comparative Physiology of the CSF and the Brain Barriers The Intracranial or CSF Pressure References Index

533 citations


Journal ArticleDOI
TL;DR: It is found that CSF βA4 1-42 level is lower in AD patients compared with non-demented controls, although there was a significant overlap between the groups.

533 citations


Journal ArticleDOI
TL;DR: It is demonstrated that neurotrophic factors can be continuously delivered within the CSF of humans by an ex vivo gene therapy approach, opening new avenues for the treatment of neurological diseases.
Abstract: Neuronal growth factors hold promise for providing therapeutic benefits in various neurological disorders. As a means of ensuring adequate central nervous system delivery of growth factors and minimizing significant adverse side effects associated with systemic delivery methods, we have developed an ex vivo gene therapy approach for protein delivery using encapsulated genetically modified xenogeneic cells. Ciliary neurotrophic factor (CNTF) has been shown in various rodent models to reduce the motor neuron cell death similar to that seen in amyotrophic lateral sclerosis (ALS). The initial trials focusing on the systemic administration of CNTF for ALS have been discontinued as a result of major side effects, thus preventing determination of the potential efficacy of the molecule. In order to deliver CNTF directly to the nervous system, we conducted a phase I study in which six ALS patients were implanted with polymer capsules containing genetically engineered baby hamster kidney cells releasing approximately 0.5 microgram of human CNTF per day in vitro. The CNTF-releasing implants were surgically placed within the lumbar intrathecal space. Nanogram levels of CNTF were measured within the patients' cerebrospinal fluid (CSF) for at least 17 weeks post-transplantation, whereas it was undetectable before implantation. Intrathecal delivery of CNTF was not associated with the limiting side effects observed with systemic delivery. These results demonstrate that neurotrophic factors can be continuously delivered within the CSF of humans by an ex vivo gene therapy approach, opening new avenues for the treatment of neurological diseases.

449 citations



Journal ArticleDOI
TL;DR: CSF velocity MR imaging is useful in the selection of patients with NPH to undergo shunt formation, and the relationship between CSF stroke volume greater than 42 microL and favorable response to VP shunting was statistically significant.
Abstract: PURPOSE: To evaluate magnetic resonance (MR) imaging-based quantitative phase-contrast cerebrospinal fluid (CSF) velocity imaging for prediction of successful shunting in patients with normal-pressure hydrocephalus (NPH). MATERIALS AND METHODS: Eighteen patients (mean age, 73 years) with NPH underwent routine MR imaging and CSF velocity MR imaging before ventriculoperitoneal (VP) shunting. The calculated CSF stroke volume and the aqueductal CSF flow void score were compared with the surgical results. RESULTS: All 12 patients with CSF stroke volumes greater than 42 microL responded favorably to CSF shunting. Of the six patients with stroke volumes of 42 microL or less, three improved with shunting while three did not. The relationship between CSF stroke volume greater than 42 microL and favorable response to VP shunting was statistically significant (P < .05). There was no statistically significant relationship between aqueductal CSF flow void score and responsiveness to shunting. CONCLUSION: CSF velocity ...

354 citations


Journal ArticleDOI
TL;DR: The decreased CSF volume that results from increased abdominal pressure, such as with obesity or pregnancy, may produce more extensive neuraxial blockade through diminished dilution of anesthetic.
Abstract: Background Although the cerebrospinal fluid (CSF) is the pathway of anesthetic delivery and the diluent for neuraxially administered drugs, little is known about its volume, including variability among individuals, longitudinal distribution, or influence of body habitus. Models made to investigate subarachnoid anesthetic distribution lack valid dimensions. CSF volume was measured in volunteers, and the effect of obesity and abdominal compression on CSF volume was evaluated using magnetic resonance imaging. Methods Low thoracic and lumbosacral axial magnetic resonance images of 25 healthy volunteers were obtained at 8-mm intervals by fast spin-echo sequence, which highlights CSF. A repeat image series was performed in 15 subjects during external abdominal compression. In two subjects, images were obtained without compression for the entire vertebral column. Dural sac and spinal cord areas were determined in a blinded fashion for each image using video/digital analysis. Area of the sac minus area of the cord constituted area of CSF and roots ("CSF/root"); this area multiplied by 8 mm resulted in CSF/root volume per section. Results There is great interindividual variability in CSF/root volume. From the T11-T12 disc to the sacral terminus of the dural sac, the mean volume for all subjects is 49.9 +/- 12.1 ml (mean +/- SD; range 28.0-81.1 ml). This volume was significantly less in relatively obese subjects (42.9 +/- 9.5 ml) than in nonobese subjects (53.5 +/- 12.9 ml). Abdominal compression decreased CSF/root volume by 3.6 +/- 3.2 ml. Sections through intervertebral foramina showed the biggest decrease with abdominal compression, with a lesser change in sections with veins and no change in the absence of these anatomic features. Total vertebral CSF/root volume in two subjects was 94.84 and 120.01 ml, respectively. Conclusions CSF volume is widely variable between individuals. The decreased CSF volume that results from increased abdominal pressure, such as with obesity or pregnancy, may produce more extensive neuraxial blockade through diminished dilution of anesthetic. The mechanism by which increased abdominal pressure decreases CSF volume is probably inward movement of soft tissue in the intervertebral foramen, which displaces CSF.

240 citations


Journal ArticleDOI
TL;DR: The production of IL-6 within the injured brain may likely contribute to the release of neurotrophic factors by astrocytes, as indicated by the clinical outcome of the patients.

237 citations


Journal ArticleDOI
TL;DR: The findings demonstrate that biochemical alterations are associated with aging in the frontal gray matter and there might be an increase in the brain density as indicated by increased metabolite concentrations and decreased brain water content with aging.

219 citations


Journal ArticleDOI
TL;DR: The volume of the cranial CSF, as determined by MR image-based computerized segmentation, is considerably larger than traditionally accepted and resides mostly extraventricularly, although evolving changes and growth of the head with age tend to confound the results.
Abstract: Magnetic resonance (MR) image-based computerized segmentation was used to measure various intracranial compartments in 49 normal volunteers ranging in age from 24 to 80 years to determine age-related changes in brain, ventricular, and extraventricular cerebrospinal fluid (CSF) volumes. The total intracranial volume (sum of brain, ventricular, and extraventricular CSF) averaged 1469 +/- 102 cm3 in men and 1289 +/- 111 cm3 in women. The difference was attributable primarily to brain volume, which accounted for 88.6% of the respective intracranial volumes in both sexes, but was significantly larger in men (1302 +/- 112 cm3) than in women (1143 +/- 105 cm3). In both, the cranial CSF volume averaged 11.4%. Total intracranial volume did not change with age, although the normalized brain volume of both men and women began to decrease after the age of 40 years. This decrease was best reflected by expansion of the extraventricular CSF volume which, after the age of 50 years, was more marked in men than in women. The volume of the cranial CSF, as determined by MR image-based computerized segmentation, is considerably larger than traditionally accepted and resides mostly extraventricularly. Expansion of CSF volume with age provides a good index of brain shrinkage although evolving changes and growth of the head with age tend to confound the results.

211 citations


Journal ArticleDOI
TL;DR: It is concluded that 44% of head injury survivors may develop posttraumatic ventriculomegaly, and those patients who may benefit from shunt placement are identified.
Abstract: ✓ Cerebrospinal fluid (CSF) dynamics were correlated to the changes in ventricular size during the first 3 months posttrauma in patients with severe head injury (Glasgow Coma Scale score ≤ 8, 75 patients) to distinguish between atrophy and hydrocephalus as the two possible causes of posttraumatic ventriculomegaly Using the bolus injection technique, the baseline intracranial pressure (ICP), pressure volume index, and resistance for CSF absorption (R0) provided a threedimensional profile of CSF dynamics that was correlated with ventricular size and Glasgow Outcome Scale (GOS) score at 3, 6, and 12 months posttrauma Patients were separated into five different groups based on changes in ventricular size, presence of atrophy, and CSF dynamics Group 1 (normal group, 413%) demonstrated normal ventricular size and normal ICP Group 2 (benign intracranial hypertension group, 147%) showed normal ventricular size and elevated ICP Group × (atrophy group, 24%) displayed ventriculomegaly, normal ICP, and normal

Journal ArticleDOI
TL;DR: It is shown that the flow of cerebrospinal fluid and the disposition of its constituents is fairly complex and differs among regions, and that the old concept of a "cerebro Spinal fluid-brain barrier may hold at such places.

Journal ArticleDOI
TL;DR: These functions showed that a sudden influx of blood into the head was rapidly accommodated by some type of intracranial reserve or capacity, and an equal volume of CSF was driven through the foramen magnum over the next 200‐300 ms as the intrac Cranial reserve relaxed to its base‐line state.
Abstract: Brain and cerebrospinal fluid (CSF) movements are influenced by the anatomy and mechanical properties of intracranial tissues, as well as by the waveforms of driving vascular pulsations. The authors analyze these movements so that the purely hemodynamic factors are removed and the underlying mechanical couplings between brain, CSF, and the vasculature are characterized in global fashion. These measurements were used to calculate a set of impulse response functions or modulation transfer functions, characterizing global aspects of the vasculature's mechanical coupling to the intracranial tissues, the cervical CSF, and the cervical spinal cord. These functions showed that a sudden influx of blood into the head was rapidly accommodated by some type of intracranial reserve or capacity. After this initial response, an equal volume of CSF was driven through the foramen magnum over the next 200-300 ms as the intracranial reserve relaxed to its base-line state.

Journal ArticleDOI
TL;DR: It is shown that the arrangements of venous plexuses within the vertebral canal provide anatomical preconditions for a cooling of the spinal cord via the CSF, and the possibility of spinal cord and spinal ganglia cooling by temperature convection via venous blood is discussed.
Abstract: Vascular arrangements allowing a bulky transfer of venous blood from the skin of the head and from nasal and paranasal mucous membranes to the dura matter provide an excellent anatomical basis for the convection process of cooling, caused by evaporation of sweat or mucus. The dura mater, with its extraordinarily high vascularization controlled by a potent vasomotor apparatus, may transmit temperature changes to the cerebrospinal fluid (CSF) compartment. Temperature gradients of the CSF may in turn influence the temperature of brain parenchyma (1) directly, along the extensive contact area between the cerebrocortical surface and the CSF-compartment, or (2) indirectly, via brain arteries that extend over long distances and arborize within the subarachnoid space before entering the pial vascular network and brain parenchyma. Numerous subarachnoid and pial arterial branches exposed to the CSF have diameters in the range of the vessels of the retia mirabilia of animals in which selective brain cooling has been clearly established experimentally. It is also shown that the arrangements of venous plexuses within the vertebral canal provide anatomical preconditions for a cooling of the spinal cord via the CSF. The possibility of spinal cord and spinal ganglia cooling by temperature convection via venous blood--cooled in the venous networks of the skin of the back--flowing through numerous anastomoses to the external and internal vertebral plexuses and, finally, into the vascular bed of the spinal dura is discussed on the basis of anatomical facts.

Journal ArticleDOI
TL;DR: The C system becomes activated intrathecally in SAH and focally in the brain parenchyma in ischemic stroke by promoting chemotaxis and vascular perturbation, which may instigate nonimmune inflammation and aggravate CNS damage in diseases associated with plasma extravasation.
Abstract: The central nervous system (CNS) is virtually isolated from circulating immunological factors such as complement (C), an important mediator of humoral immunity and inflammation. In circulation, C is constantly inhibited to prevent attack on host cells. Since a host of diseases produce an abnormal blood-brain/cerebrospinal fluid (blood-brain/CSF) permeability allowing C protein extravasation, we investigated if C activation occurs in CSF in vitro and in CNS in vivo during subarachnoid hemorrhage (SAH) or brain infarction. After SAH (n = 15), the terminal complement complex (TCC) concentration on days 0 to 2 was higher in the CSF, 210 +/- 61 ng/ml, than in the plasma, 63 +/- 17 ng/ml, but null in the CSF of controls (n = 8) or patients with an ischemic stroke (n = 7). TCC was eliminated from the CSF after SAH (24 +/- 10 ng/ml on days 7 to 10). Incubation of normal human CSF with serum in vitro also activated the terminal C pathway. In 10 fatal ischemic brain infarctions, immunohistochemical techniques demonstrated neuronal fragment-associated deposition of C9 accompanied by neutrophil infiltration. We conclude that the C system becomes activated intrathecally in SAH and focally in the brain parenchyma in ischemic stroke. By promoting chemotaxis and vascular perturbation, C activation may instigate nonimmune inflammation and aggravate CNS damage in diseases associated with plasma extravasation.

Journal ArticleDOI
TL;DR: The soluble form of Alzheimer's amyloid beta protein is associated with high density lipoproteins (HDL) in normal human plasma and exhibited an N-terminal sequence identical to the A beta peptide with a mass of 4325.1 Da, indicating that the main sA beta specie associated with CSF-HDL is A beta 1-40.

Journal ArticleDOI
TL;DR: It is reported here that recombinant OB protein binds specifically to the choroid plexus and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats.
Abstract: Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor.

Journal ArticleDOI
TL;DR: At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of r CBF.
Abstract: OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.

Journal ArticleDOI
TL;DR: A computerised infusion test to compensate for the disadvantages of Katzman's lumbar infusion method: inadequate accuracy of estimation of the resistance to cerebrospinal fluid outflow and poor predictive value in normal pressure hydrocephalus.
Abstract: OBJECTIVE--To design a computerised infusion test to compensate for the disadvantages of Katzman's lumbar infusion method: inadequate accuracy of estimation of the resistance to cerebrospinal fluid outflow and poor predictive value in normal pressure hydrocephalus. METHODS--Accuracy was improved by intracranial pressure signal processing and model analysis for measurement of cerebrospinal compensatory variable. These include the CSF outflow resistance, brain compliance, pressure-volume index, estimated sagittal sinus pressure, CSF formation rate, and other variables. Infusion may be made into the lumbar space, ventricles, or, when assessing shunt function in vivo, the shunt chamber. RESULTS AND CONCLUSIONS--The computerised test has been used for five years in a multicentre study in 350 hydrocephalic patients of various ages, aetiologies, and states of cerebrospinal compensation. The principles of using the test to characterise different types of CSF circulatory disorders in patients presenting with ventricular dilatation, including brain atrophy and normal and high pressure hydrocephalus, are presented and illustrated. Previous studies showed a positive correlation between cerebrospinal compensatory variables and the results of shunting, but such a prediction remains difficult in idiopathic normal pressure hydrocephalus, particularly in elderly patients. The technique is helpful in the assessment of shunt malfunction, including posture-related overdrainage, over-drainage related to the nocturnal B wave activity, and proximal or distal shunt obstruction. The appendix presents an introduction of the mathematical modelling of CSF pressure volume-compensation included in computerised infusion test software.

Journal ArticleDOI
TL;DR: It is concluded that the clearance of 125I‐HSA from the CSF is almost equally distributed between lymphatic and arachnoid villi pathways.
Abstract: We investigated lymphatic drainage pathways of the central nervous system in conscious sheep and quantified the clearance of a cerebrospinal fluid (CSF) tracer into lymph and blood. In the first group of studies, 125I-HSA was injected into the lateral ventricles of the brain or into lumbar CSF and after 6 h, various lymph nodes and tissues were excised and counted for radioactivity. Multiple lymphatic drainage pathways of cranial CSF existed in the head and neck region defined by elevated 125I-HSA in the retropharyngeal/cervical, thymic, pre-auricular and submandibular nodes. Implicated in spinal CSF drainage were mainly the lumbar and intercostal nodes. In a second group of experiments, multiple cervical vessels and the thoracic duct were cannulated and lymph diverted from the animals. Transport of tracer through arachnoid villi was taken from recoveries in venous blood. Following intraventricular administration, the 6 h recoveries of 125I-HSA in the lymph (sum of cervical and thoracic duct) and blood were 8.2% +/- 3.0 and 12.5% +/- 4.5 respectively and at 22 h, 25.1% +/- 6.9 and 20.8% +/- 4.1 respectively. When 125I-HSA was injected into lumbar CSF, the 6 h recoveries of tracer in thoracic duct and blood were 11.6% +/- 2.7 and 16.3% +/- 3.7 respectively. Total lymph and blood recoveries were not significantly different in any experiment. We conclude that the clearance of 125I-HSA from the CSF is almost equally distributed between lymphatic and arachnoid villi pathways.

Journal ArticleDOI
TL;DR: The enantiospecific occurrence of (R)‐N‐methylsalsolinol in cerebrospinal fluid suggests its enzymatic synthesis in the human brain, which might be involved in the pathogenesis of Parkinson's disease.
Abstract: The concentration of (R)-N-methylsalsolinol, which is a dopamine-derived neurotoxin selective to dopamine neurons and induces parkinsonism in rats, was found to be increased significantly in the cerebrospinal fluid of untreated patients with Parkinson's disease. The enantio-specific occurrence of (R)-N-methylsalsolinol in cerebrospinal fluid suggests its enzymatic synthesis in the human brain. The individual differences in the activities of the enzymes determining the metabolism of (R)-N-methylsalsolinol in the brain might be involved in the pathogenesis of Parkinson's disease.

Journal ArticleDOI
TL;DR: The results suggest that the presence of sFas possibly leads to cell death/neurodegeneration in parkinsonian brain.

Journal ArticleDOI
TL;DR: Simultaneous hindrance of principal and collateral venous outflow will lead to elevated venous pressure and eventual insufficiency of cerebral blood flow (CBF), which will cause increased intracranial pressure, and ventricular enlargement due to periventricular atrophy.
Abstract: For more than a century, available data concerning collateral venous outflow from the brain have received insufficient attention, as existing theories did not assign practical importance to them. Ideas concerning arterial blood supply and circulation of cerebrospinal fluid were considered more relevant. But available data afford a schematic model of cerebral venous outflow that does have important pathophysiological consequences. Principal outflow through the internal jugular veins can be substituted completely by the large vertebral plexuses, through communications at the cranial base. Emissary veins of the skull vault are small and few in number. Outflow from the deep venous system through the great vein of Galen can be substituted by choroidal, thalamic and striate anastomoses toward the basal vein. So-called intracerebral venous anastomoses through the centrum semiovale towards the convexity are nonexistent or negligible. Instead, a venous watershed exists separating paraventricular white matter from a layer of subcortical white matter. In most infants, the cavernous sinus is not yet connected to the cerebral veins. Once such communications have been formed, important collateral pathways exist through basal and Sylvian veins via the cavernous sinus to the pterygoid plexuses. Simultaneous hindrance of principal and collateral venous outflow will lead to elevated venous pressure and eventual insufficiency of cerebral blood flow (CBF). This will cause increased intracranial pressure, and ventricular enlargement due to periventricular atrophy. The slow phase of the two-compartment model of CBF coincides with the paraventricular white matter area of the deep venous system. In the neonate CBF was found to be still very low, and in the two compartments CBF increases at a different rate to a maximum in childhood. In hydrocephalus, measurement of CBF in the slow deep compartment, rather than the fast cortical one, will be most informative.

Journal ArticleDOI
TL;DR: Data show that azithromycin appears to be widely distributed into brain tissue but not into cerebrospinal fluid or aqueous humor of the eye.
Abstract: To measure the concentrations of azithromycin in the central nervous system, 20 patients with brain tumors (group I) received a single 500-mg oral dose of azithromycin either 24, 48, 72, or 96 h prior to the tumor removal operation and 10 patients with cataracts undergoing surgery (group II) and 7 patients scheduled to undergo lumbar puncture (group III) received the same dose of azithromycin 24 h prior to the operation or procedure. Serum from all patients, brain tissue from group I, aqueous humor from group II, and cerebrospinal fluid from group III were assayed for azithromycin concentration. The mean concentrations of azithromycin in brain tissue 24, 48, 72, and 96 h after administration were 2.63 +/- 2.58, 3.64 +/- 3.81, 0.74 +/- 0.37, and 0.41 micrograms/g, respectively. In contrast, the concentrations of azithromycin in cerebrospinal fluid and aqueous humor of the eye were very low or undetectable. Therefore, these data show that azithromycin appears to be widely distributed into brain tissue but not into cerebrospinal fluid or aqueous humor of the eye.

Journal ArticleDOI
TL;DR: Pregnancy and the immediate postpartum period are associated with the lowest CSF densities, and the cutoff values defining hypobaricity (mean CSF density minus three standard deviations) are greater than previously reported.
Abstract: Background Dextrose-free local anesthetics and opioids, alone and in combinations, are being used increasingly to provide subarachnoid anesthesia and analgesia These dextrose-free drugs have been described as hypobaric by some and isobaric by others To accurately classify anesthetics with regard to baricity, the density of cerebrospinal fluid (CSF) must be known The authors sought to determine the exact density of human CSF, and determine whether CSF density is altered by pregnancy Methods Density measurements accurate to 000001 g/ml were made at 3700 degrees C, using a mechanical oscillation resonance frequency density meter Cerebrospinal fluid samples were obtained from 44 patients during spinal anesthesia Five groups were studied: men, and premenopausal, postmenopausal, term pregnant, and postpartum women Results Mean CSF densities in men (100064 +/- 000012 g/ ml), postmenopausal women (100070 +/- 000018 g/ml), and nonpregnant premenopausal women (100049 +/- 000004 g/ ml) were significantly greater than in term pregnant (100030 +/- 000004 g/ml) and postpartum (100034 +/- 000005 g/ml) women Cerebrospinal fluid density did not correlate with age Conclusions Mean CSF density varies in different patient subpopulations Pregnancy and the immediate postpartum period are associated with the lowest CSF densities In addition, the cutoff values defining hypobaricity (mean CSF density minus three standard deviations) are greater than previously reported Accurate CSF density values should be used when considering baricity as a mechanism for clinical observations of dextrose-free intrathecal local anesthetics and opioids Gestational status also should be considered

Journal ArticleDOI
TL;DR: The findings suggest that the local production of the alpha-chemokines IL-8 and GRO-alpha and of the beta-chemOKine MCP-1 represents the major chemoattractant stimulus for the differential recruitment of leukocytes into the subarachnoid space during meningitis.

Journal ArticleDOI
TL;DR: The choroid plexus is characterized as a paracrine, growth-promoting organ for the developing cerebellum, with the effects mediated through temporally regulated RA production.

Journal ArticleDOI
TL;DR: Post mortem brains were examined for the presence of fibrin(ogen) and its cleavage products by two dimensional gel electrophoresis followed by immunoblotting and these results suggest that a CNS inflammatory process may be occurring in a subgroup of schizophrenic patients.

Journal Article
TL;DR: Investigation of the effect of IL-10 on regional cerebral blood flow, intracranial pressure, cerebrospinal fluid (CSF) white blood cell count, and brain water content within 6 h after intracisternal (i.c.c.) pneumococcal challenge in a rat model of meningitis found suppression of nitrite concentration in cell culture supernatant of primary rat cerebral endothelial cells when stimulated with heat-killed pneumococci.
Abstract: IL-10, a potent immunosuppressive cytokine, leads to macrophage/monocyte deactivation, inhibiting the production of cytokines and the release of reactive oxygen species and reactive nitrogen intermediates, which are known to be involved in the pathophysiology of bacterial meningitis. We investigated the effect of IL-10 on regional cerebral blood flow, intracranial pressure, cerebrospinal fluid (CSF) white blood cell count, and brain water content within 6 h after intracisternal (i.c.) pneumococcal challenge in a rat model of meningitis. Compared with IL-10 vehicle-injected infected rats, i.p. administration of 5 microg of IL-10 significantly attenuated the increase in regional cerebral blood flow, brain water content, intracranial pressure, and CSF white blood cell count, whereas a lower dosage of IL-10 (0.5 microg) was ineffective. The inhibitory effect of IL-10 (5 microg) was observed irrespective of time of IL-10 administration: just before, 1 h after, or 4 h after pneumococcal challenge. In contrast, i.c. application of IL-10 (5 microg) did not modulate these pathophysiologic parameters, and even augmented CSF pleocytosis. Moreover, i.c. injection of IL-10 alone induced meningeal inflammation in uninfected rats. IL-10 injected i.p., but not i.c., markedly inhibited the increase in IL-6 levels, as determined in CSF of infected animals. IL-10 suppressed the increase of nitrite concentration in cell culture supernatant of primary rat cerebral endothelial cells when stimulated with heat-killed pneumococci. The possible modes of action of IL-10 in pneumococcal meningitis may involve its interference with the production of nitric oxide or IL-6.

Journal ArticleDOI
TL;DR: Artificial CSF used as a physiological perfusate during endoneurosurgery can suppress host reactions within the CSF pathway and is also available for routine neurosurgical procedures.
Abstract: To compare the benefits of physiological saline solution and artificial cerebrospinal fluid (CSF) as perfusates, we investigated 12 patients with presumed symptomatic aqueductal stenosis by clinical course and CSF analysis. In all patients, endoneurosurgical third ventriculostomy and cine magnetic resonance imaging confirmed the patency of ventriculostomy. After endoneurosurgery, patients who received the saline solution experienced high fever, headaches, and elevated cell count in lumbar CSF. Saline solution provoked a striking inflammatory reaction in the CSF. In contrast, the artificial CSF reduced these conditions to a minimum. Artificial CSF used as a physiological perfusate during endoneurosurgery can suppress host reactions within the CSF pathway and is also available for routine neurosurgical procedures.