Investigation of Cerebrospinal Fluid Electrolytes and Acid-Base Expressions in Asian Adults.

BACKGROUND: In previous literature, reference values for cerebrospinal fluid (CSF) may be based on patients who were not truly healthy, other species, or outdated information. In the present study, we performed a lumbar puncture in patients requiring spinal anesthesia by a reasonable indication to evaluate CSF parameters in healthy adults. METHODS: All patients between the ages of 20 and 70 years scheduled for elective orthopedic or urologic surgery requiring spinal anesthesia were enrolled in this study. We measured electrolytes and gas tension analysis in CSF and whole blood samples in adult humans. RESULTS: A total of 28 patients were included with an average age of 44.2 years. The concentration of Na^+ in blood was slightly lower when compared with that in CSF. There were significantly higher levels of K^+ and Ca^(2+) in the blood when we compared with CSF. Significantly lower levels of Cl^- and Mg^(2+) in the blood were observed when compared with CSF. The glucose level of CSF was about half of that in blood. CONCLUSIONS: We provided updated reference values for various solutes in blood and CSF in adults. Analysis of CSF parameters and relevant paired blood samples is highly informative, helping clinicians diagnose a variety of central nervous system diseases.

SOX9-COL9A3-dependent regulation of choroid plexus epithelial polarity governs blood-cerebrospinal fluid barrier integrity.

The choroid plexus (CP) is an extensively vascularized neuroepithelial tissue that projects into the brain ventricles. The restriction of transepithelial transport across the CP establishes the blood-cerebrospinal fluid (CSF) barrier that is fundamental to the homeostatic regulation of the central nervous system microenvironment. However, the molecular mechanisms that control this process remain elusive. Here we show that the genetic ablation of Sox9 in the hindbrain CP results in a hyperpermeable blood-CSF barrier that ultimately upsets the CSF electrolyte balance and alters CSF protein composition. Mechanistically, SOX9 is required for the transcriptional up-regulation of Col9a3 in the CP epithelium. The reduction of Col9a3 expression dramatically recapitulates the blood-CSF barrier defects of Sox9 mutants. Loss of collagen IX severely disrupts the structural integrity of the epithelial basement membrane in the CP, leading to progressive loss of extracellular matrix components. Consequently, this perturbs the polarized microtubule dynamics required for correct orientation of apicobasal polarity and thereby impedes tight junction assembly in the CP epithelium. Our findings reveal a pivotal cascade of SOX9-dependent molecular events that is critical for construction of the blood-CSF barrier.

Electrolytes and Biochemical Changes in Cerebrospinal Fluid in Drowning: Experimental Rabbit Model.

The diagnosis of drowning is still a difficult task in forensic science. Biochemical changes in different body fluids have been examined for the identification of drowning. However, none of them alone gives accurate results in the diagnosis of drowning and differentiation of saltwater and freshwater drowning. This study aimed to examine cerebrospinal fluid changes in drowned rabbits. Six groups of rabbits were used including immersed dead rabbits in freshwater or saltwater (as control groups), alive fully conscious rabbits drowned in freshwater and saltwater, and anesthetized rabbits drowned in freshwater and saltwater. Cerebrospinal fluid electrolytes except for potassium levels were significantly higher in rabbits drowned consciously in saltwater than their level in the control group. In rabbit drowned in freshwater, the examined electrolytes decreased significantly. In addition, urea, creatinine, uric acid, glucose, and tumor necrosis factor were different in cases of freshwater and saltwater drowning from those of control rabbits. Electrolytes and biochemical changes of unconscious rabbits drowned in water showed no significant difference from those of control rabbits. Cerebrospinal fluid examination in drowning gives promising results in the diagnosis of drowning. In addition, the differentiation between freshwater and saltwater drowning was possible.

Time-dependent changes in epidural catheter aspirate after injection of a local anesthetic.

STUDY OBJECTIVE: A glucose check is used for investigation of a suspected accidental dural puncture in epidural anesthesia. However, glucose-positive clear fluid is sometimes aspirated from an epidural catheter in cases without clinical evidence of puncture. The goal of the study was to investigate time-dependent changes in the aspirate composition after injection of a local anesthetic into the epidural space. DESIGN: Observational study. SETTING: Operating rooms at Hamamatsu University Hospital. PATIENTS: The subjects were 30 patients (ASA I or II) undergoing surgery with combined epidural and general anesthesia. INTERVENTIONS: After epidural injection of local anesthetics, aspiration through the catheter was performed every 10min until fluid could not be aspirated. pH, Na, K, Cl, Ca and glucose were measured in fluid samples using a blood gas analysis apparatus. MAIN RESULTS: No patients had pain or clinical signs suggesting dural puncture throughout the perioperative period. Fluid aspiration was possible in 15 patients (50%) after 10min and in 7, 3, 2 and 2 patients after 20, 30, 40 and 50min, respectively. Glucose was detected in each aspirated fluid sample and gradually increased with time to become closer to the level in cerebrospinal fluid (CSF). Each electrolyte also changed to approach the level found in CSF. CONCLUSIONS: A glucose check may increase the risk of a false-positive finding for accidental dural puncture with increasing time after local anesthetic injection. Conversely, detection of glucose at the time of epidural catheter placement may provide useful information for detection of accidental dural puncture.

The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific sulforhodamine 101-labeling of hippocampal astrocytes.

Sulforhodamine 101 (SR101) is widely used for astrocyte identification, though the labeling mechanism remains unknown and the efficacy of labeling in different brain regions is heterogeneous. By combining region-specific isolation of astrocytes followed by transcriptome analysis, two-photon excitation microscopy, and mouse genetics, we identified the thyroid hormone transporter OATP1C1 as the SR101-uptake transporter in hippocampus and cortex.

Effect of carrageenan-induced acute peripheral inflammation on the electrolyte disposition to cerebrospinal fluid in rats.

To clarify whether peripheral inflammation has a remote effect on the central nervous system, the electrolyte disposition between the circulating blood and central nervous system was evaluated in rats with carrageenan-induced acute peripheral inflammation (API). λ-Carrageenan was subcutaneously injected in the hind paw of the rat, and lithium was utilized as a surrogate marker of sodium. When the plasma and cerebrospinal fluid (CSF) concentrations of lithium were examined following lithium being intravenously administered, it was revealed that the CSF concentration of lithium in API rats is reduced compared to that in normal rats, while the plasma concentration profile of lithium in API rats is indistinguishable from that in normal rats. The pharmacokinetic analysis showed that the lithium disposition from the plasma to CSF markedly decreased by 35.8% in API rats compared to that in normal rats. On the other hand, when lithium was immediately administered into the lateral ventricle, its elimination profiles in CSF were not different between normal and API rats. It is therefore probable that the lithium disposition from the plasma to CSF alters in API rats, reflecting the entry process of electrolytes from the circulating blood to brain tissue being suppressed in response to peripheral inflammation.

Altered electrolyte handling of the choroid plexus in rats with glycerol-induced acute renal failure.

The altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na(+) /K(+) /2Cl(-) co-transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na(+) /H(+) exchanger and ouabain for Na(+) /K(+) -ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na(+) /K(+) /2Cl(-) co-transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted.

Spinal anaesthesia with 0.5% isobaric bupivacaine in patients with diabetes mellitus: the influence of CSF composition on sensory and motor block.

BACKGROUND AND OBJECTIVE: We investigated cerebrospinal fluid characteristics in patients with and without diabetes mellitus and the influences that changes in these characteristics have on sensory and motor block when spinal anaesthesia is performed. METHODS: We included 44 patients in each study group. All received spinal administration of 15 mg of 0.5% isobaric bupivacaine. Blood and cerebrospinal fluid were analysed for glucose, total protein, urea, albumin, immunoglobulin G, sodium, chloride, potassium, calcium, magnesium and osmolarity as well as the performance of the local anaesthetic from establishment until complete regression of sensory and motor block. RESULTS: The cerebrospinal fluid of the two groups differed significantly (P < 0.05) in the levels of total protein, albumin, immunoglobulin G, glucose and osmolarity. Sensory and motor block was established more rapidly in the diabetic group (P < 0.05), and the total duration from maximum block until regression to two dermatomes was greater (P < 0.05), as was the complete regression from sensory and motor block (P < 0.05). CONCLUSION: This study shows that diabetes mellitus has an influence on sensory and motor block after the administration of spinal isobaric bupivacaine.

Scn2a sodium channel mutation results in hyperexcitability in the hippocampus in vitro.

PURPOSE: To investigate in vitro, the cellular network activity of the hippocampus in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene. METHODS: Extacellular recordings were obtained from CA1 and CA3 pyramidal neurons in hippocampal slices prepared from Q54 transgenic and nontransgenic littermates (WT) under physiologic conditions as well as during periods of orthodromic stimulation of the Schaffer collaterals. Cerebral spinal fluid samples were analyzed and cresyl violet histology of the hippocampus was conducted. RESULTS: Increased spontaneous extracellular activity was found in both CA1 and CA3 regions of Q54 hippocampal slices. Q54 slices also demonstrated significantly greater spontaneous and afterdischarge activity as well as population spike amplitude and duration following tetanic stimulus in comparison to WT slices. Frequency analysis of tetanically stimulated recordings indicated high-frequency components (100 and 200 Hz) unique to Q45 slices. Analysis of cresyl violet histology supports healthy Q54 slices up to 10 weeks, while Q54 cerebral spinal fluid shows elevated osmolarity. CONCLUSION: Evidence for hyperexcitability and increased synaptic efficacy in Q54 mice was found by observing spontaneous activity as well as evoked activity. Response to tetanic stimulation included unique high-frequency oscillations, and resulted in an increased population spike amplitude and duration. Histological assessment shows equivalent neuronal development in both experimental groups. The data support the hypothesis that modified Scn2a channels in Q54 mice result in network hyperexcitability of the hippocampus necessary for the development and maintenance of temporal lobe seizures.

Estimation of time since death from CSF electrolyte concentration in Bhopal region of central India.

Estimation of time since death from sodium and potassium ion concentration levels in CSF (cerebrospinal fluid) was carried out in 100 medico legal autopsies with known time of death in the department of Forensic medicine, Gandhi Medical College in Bhopal region of Central India. CSF was aspirated from lateral ventricles after opening the skull and dura, and concentration of these ions were estimated by flame photometry. Results revealed a significant correlation of sodium and potassium ions in CSF up to 25 h of time since death, with average per hour rise of 1.21 meq/h for potassium and fall of 1.115 meq/h for sodium ions. A useful relationship between sodium potassium ion ratio and PMI (post-mortem interval) was also elicited. The study concludes that changes in CSF electrolyte is a significant parameter to estimate time since death.

Prolonged elevation of magnesium in the cerebrospinal fluid of patients with severe head injury.

OBJECTIVES: Several works have investigated the role of serum magnesium (Mg) concentrations in traumatic brain injury. However, there is restricted information about cerebrospinal fluid (CSF) levels of Mg in patients with severe head injury (SHI). We assessed the changes of Mg concentrations in CSF and serum in patients with SHI during the first 10 days after the trauma. METHODS: Eleven patients with SHI were studied prospectively on days 1-3, 5 and 10 with analysis of CSF and serum levels of Mg and Ca. The control group consisted of nine patients with hydrocephalus. RESULTS: CSF levels of Mg were significantly higher in patients than controls in the corresponding time points except on days 5 and 10 of trauma. The CSF Mg levels tended to decrease and the highest level was found on day 1 after trauma (2.81 +/- 0.65 mg/dl). In the control group, the CSF level of Mg was 1.95 +/- 0.66 mg/dl. No significant difference can be detected between controls and patients regarding serum Mg and Ca levels. In addition, significantly higher values of Ca in the CSF were observed in all time points after trauma in patients with SHI than in the controls. There was no correlation between the CSF and serum levels of Mg and Ca levels. DISCUSSION: Our study demonstrates that in patients with SHI, CSF levels of Mg and Ca are elevated during the whole observation period. Further works should be designed in order to show the role and importance of CSF levels of ionized Mg in outcome of patients with SHI.

[Cerebral microdialysis in stroke]. / Zerebrale Mikrodialyse beim Schlaganfall.

Cerebral microdialysis is an invasive technique for neurochemical monitoring that has been established for neuro-critical disorders such as subarachnoid hemorrhage and severe brain injury. We present data on cerebral microdialysis in stroke patients which were obtained in an ongoing study supported by the German Ministry for Education and Research. So far, 50 patients have been included who required critical care due to massive stroke of the middle cerebral artery territory. By correlating the microdialysis results with follow-up CT scans, we could define the neurochemical characteristics of three different brain compartments: (1) noninfarcted brain tissue with normal microdialysis values, (2) brain areas adjacent to the infarct core which were not hypodense in CT scans but caused reversible neurochemical alterations, and (3) the infarct core with massive concentration changes which did not normalize over the measuring period of 3 to 5 days. Microdialysis values averaged over time and correlated with initial PET scans helped to describe neurochemical predictors of a malignant, i.e., life-threatening, space-occupying course of the ischemic stroke. We discuss the value of this method in guiding therapy and predicting clinical outcome in the context of other neurological critical care disorders and describe the pros and cons of cerebral microdialysis as an invasive monitoring technique.

Differential effects of diabetes on rat choroid plexus ion transporter expression.

Though diabetes is a disease with vascular complications, little is known about its effects on the blood-brain barrier or the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is situated at choroid plexuses located in the lateral, third, and fourth ventricles. Choroid plexuses are the primary site of cerebrospinal fluid (CSF) production and express numerous ion transporters. Previous studies have shown a perturbation of ion transport in the periphery and brain during diabetes. In this study, we investigated the effect of diabetes on ion transporters in the choroid plexuses of streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of STZ (60 mg/kg in citrate buffer, confirmed by glucose analysis: 601 +/- 22 mg/dl diabetic rats, 181 +/- 46 mg/dl age-matched controls); and at 28 days, rats were killed, choroid plexuses harvested, and protein extracted. Western blot analyses were carried out using antibodies for ion transporters, including Na(+)-K(+)-2Cl(-) cotransporter and the Na(+)-K(+)-ATPase alpha1-subunit. The efflux of the K(+) analog (86)Rb(+) from choroid plexus was also studied. Diabetic rats showed an increase in expression of the Na(+)-K(+)-2Cl(-) cotransporter and the Na(+)-K(+)-ATPase alpha1-subunit, as compared with age-matched controls, a decrease in Na(+)-H(+) exchanger expression, and no change in Na(+)-K(+)-ATPase beta1- or beta2-subunit. The net effect of these changes was a 66% increase in (86)Rb(+) efflux from diabetic choroid plexus compared with controls. These changes in expression may affect choroid plexus ion balance and thus significantly affect CSF production in diabetic rats.

Rectal temperature and prostaglandin E2 increase in cerebrospinal fluid of conscious rabbits after intracerebroventricular injection of hemoglobin.

Fever accompanies subarachnoid hemorrhage (SAH) in the majority of patients. In a previous study, hemoglobin (Hb) was shown to catalyze in vitro, under aerobic conditions, the conversion of arachidonic acid to prostaglandin E2 (PGE2) and prostaglandin F2alpha. The aim of the present work was to assess whether this pathway also operates in vivo and to provide a mechanism to explain post-SAH fever. To this end, PGE2 concentration was determined in cerebrospinal fluid (CSF) of conscious rabbits chronically cannulated in the lateral ventricle and cisterna magna, following intracerebroventricular (i.c.v.) injection of 10 microg or 100 microg of commercial rabbit bicrystallized Hb as a model of SAH. Before i.c.v. injection, Hb solutions were filtered on a polimixin-B column to remove substantially, by over 90%, endotoxin-like substances. Results show that in nine rabbits injection of 10 microg Hb did not significantly modify body temperature or significantly alter CSF PGE2 content. On the contrary, in nine rabbits, injection of 100 microg Hb produced a significant increase in core temperature which was accompanied by a significant increase in CSF PGE2. When data related to these two parameters from the 9 control and 18 Hb-treated rabbits were analyzed as a single group, a linear, positive, and highly significant correlation was found. These findings indicate that, once Hb is released into the subarachnoid space during SAH, it enhances CSF PGE2 content and elicits hyperthermia, thus offering an explanation for the fever that is an aggravating condition in most SAH patients.

Toxicology of Astragalus lusitanicus Lam.

Astragalus lusitanicus is a toxic legume grown in Morocco and in some other Mediterranean countries. In small ruminants, poisoning by this plant is dominated by nervous signs characterized by many cycles of excitement-depression. Macroscopic examination of poisoned animals showed congestive lesions and oedema in the brain and lungs. Microscopic lesions consisted mainly of vacuolar degeneration in neurons, hepatocytes and in spleen and kidney cells. Serum activity of AST and CK as well as blood glucose and urea were increased as a result of poisoning. However, serum activity of alpha-mannosidase was not modified as is the case in locoism. Chemical investigations showed that A. lusitanicus does not contain swainsonine or miserotoxin and its selenium concentration is very low. However, this legume contains indolizidin alkaloids and a first compound was purified and identified.

Biochemical analysis of serum and cerebrospinal fluid in clinically normal adult camels (Camelus dromedarius).

The concentrations of total protein, glucose, cholesterol, triglyceride, urea nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phosphorus, copper, magnesium, and iron and the activities of aspartate aminotransferase (AST), alanine aminotransferase, (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LD), creatine kinase (CK) and amylase were determined in cerebrospinal fluid (CSF) and serum from 21 clinically healthy adult camels. The concentrations of sodium, potassium and chloride in CSF were similar to those of serum; whereas the values for all other constituents were significantly higher (P<0.05) in serum than in CSF.

Meningitis bacteriana: parte 1 / Bacterial meningitis: part 1

La meningitis bacteriana es una enfermedad de gran interés en pediatría. Su gravedad y potenciales secuelas la colocan dentro de un marco trascendental en la pediatría. Esta es una enfermedad que afecta más frecuentemente a niños menores de 5 años y en forma especial a niños menores de 1 año. El diagnóstico oportuno, la identificación del agente causal, el conocimiento de la prevalencia de resitencia bacteriana, el uso pertinente de antibióticos y medidas de sostén, están directamente relacionados con la buena evolución y la disminución de las secuelas a corto y mediano plazo. Este trabajo consiste en una revisión de los datos actuales en la etiología, diagnóstico y manejo de la meningitis bacteriana en niños. Tiene por objetivo ofrecer al lector una información completa, actualizada y aplicada a nuestro país, en cuanto a la meningitis bacteriana se refiere

Acute hyponatraemia secondary to cerebral salt wasting syndrome in a patient with tuberculous meningitis.

A 30-year-old HIV-positive man presented with acute hydrocephalus secondary to tuberculous meningitis, for which an external ventricular drain was inserted. He developed marked natriuresis in the postoperative period, which resulted in acute hyponatraemia (131 to 122 mmol/l) and a contraction of his intravascular volume. A diagnosis of cerebral salt wasting syndrome was made, and he responded to sodium and fluid loading. This case highlights the differentiation of cerebral salt wasting syndrome from the more commonly occurring syndrome of inappropriate anti-diuretic hormone secretion as the aetiology of the hyponatraemia.