[Assessment of the significance of dilated perivascular spaces and nocture arterial hypertension in the development of Alzheimer's disease]. / Otsenka znacheniya rasshirennykh perivaskulyarnykh prostranstv i nochnoi arterial'noi gipertenzii v razvitii bolezni Al'tsgeimera.

OBJECTIVE: To study the severity and localization of dilated perivascular spaces (DPVS), the levels of protein markers of amyloidosis and neurodegeneration in the cerebrospinal fluid (CSF) at different daily blood pressure (BP) profiles in patients with Alzheimer's disease (AD) and other types of cognitive impairment. MATERIAL AND METHODS: A total of 119 people, aged 53 to 92 years, including 55 patients with AD, 27 patients with vascular cognitive disorders (VCD), 19 patients with frontotemporal degeneration (FTD). All patients underwent BP monitoring for 24 hours using a standard oscillometric measurement method, lumbar puncture to assess Aß-42 and Aß-40 amyloid protein, total and phosphorylated tau protein in the CSF, magnetic resonance imaging tomography of the brain with subsequent assessment of the severity of expansion and localization of DPVS according to the G.M. Potter scale. RESULTS: In 58.3% of patients with AD, there is no adequate reduction in BP at night in comparison with patients with VCD (p<0.05). A significant degree of expansion of the DPVS turned out to be most typical for patients with AD: grade 3 was detected in 45.7% of patients, and the maximum, grade 4, was detected in 13.4%. At the same time, DPVSs were significantly more often detected in the group of subjects with insufficient reduction in diastolic BP (DBP) at night. A strong inverse correlation was established between the level of Aß-42 in the CSF and the variability of DBP at night (r= -0.92; p<0.05). The decrease in the level of Aß-42 in AD, especially at the prodromal stage, is directly related to the low variability of DBP at night, which is more characteristic of an insufficient decrease or increase in BP during night sleep. CONCLUSION: Patients with AD were characterized by an insufficient decrease in BP at night, which is associated with the severity and degree of maximum expansion of the DPVS. A decrease in the level of Aß-42 amyloid protein in the CSF strongly correlates with the variability of DBP at night.

Interleukin-6-Mediated Inflammation May Cause Methotrexate-Induced Leukoencephalopathy.

Children with leukemia treated with methotrexate (MTX) may develop MTX-induced leukoencephalopathy, which can present as seizures or focal neurological deficits. However, the precise pathophysiology has not been fully elucidated. Differences in cytokine/chemokine profiles in cerebrospinal fluid (CSF) between children with MTX-induced leukoencephalopathy and those with posterior reversible encephalopathy syndrome (PRES), an acute neurological condition associated with hypertension, were investigated. Interleukin (IL)-1ß, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17, tumor necrosis factor-alpha, interferon-gamma, granulocyte monocyte colony-stimulating factor, granulocyte colony-stimulating factor, macrophage inflammatory protein-1ß, and monocyte chemoattractant protein-1 concentrations were measured in CSF supernatants from 3 children with acute leukemia with MTX-induced leukoencephalopathy, 3 children with acute leukemia with PRES, 6 children with acute leukemia without neurological complications, and 8 children with acute encephalopathy. CSF IL-6 concentrations were higher in children with MTX-induced leukoencephalopathy than in children with acute leukemia with PRES, with acute leukemia without neurological complications, and with acute encephalopathy. We concluded that IL-6 may be involved in the pathogenesis of MTX-induced leukoencephalopathy.

Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na+] from hypertensive and normotensive human subjects with family histories of Alzheimer's disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na+] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na+] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na+], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na+] and BP but showed no correlation between plasma [Na+] and BP. In sum, CSF [Na+] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na+] in chronic hypertension in humans.

Associations Between Multimorbidity and Cerebrospinal Fluid Amyloid: A Cross-Sectional Analysis of the European Prevention of Alzheimer's Dementia (EPAD) V500.0 Cohort.

BACKGROUND: Multimorbidity (the co-occurrence of multiple chronic conditions) is increasingly common, especially among people with dementia. Few neuroimaging studies have explored amyloid biomarkers in people with multimorbidity. OBJECTIVE: We aimed to conduct the first study of the association between multimorbidity and cerebrospinal fluid amyloid-ß42 (CSF Aß). METHOD: The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study V500.0 dataset includes volunteers aged ≥50 years from 12 sites. Participants undergo detailed phenotyping, including CSF measures and a self-reported medical history. Using logistic and linear regression analyses, we explored the association between multimorbidity and continuous chronic condition count with CSF Aß positivity (Aß42 <1000pg/ml) and continuous CSF Aß concentration. All models were adjusted for age, sex, APOE status, education, and family history of dementia. RESULTS: Among 447 eligible participants without dementia, the mean (SD) age was 66.6 (6.6) years, 234 (52.3%) were women, and 157 (35.1%) were amyloid positive. With chronic conditions regarded as pseudo-continuous, each additional condition carried a decreased likelihood of amyloid positivity (OR = 0.82, 95% CI: 0.68-0.97; p = 0.026). With CSF Aß as a continuous variable, each additional condition was associated with an increase of 54.2 pg/ml (95% CI: 9.9-98.5, p = 0.017). Having ≥2 conditions was inversely associated with amyloid positivity (OR 0.59, 95% CI: 0.37-0.95, p = 0.030) compared to one or none. CONCLUSION: Our findings suggest that the established association between multimorbidity and dementia may be due to a pathway other than amyloid. However, this cross-sectional study does not allow us to make causal inferences. Longitudinal work is required to confirm the inverse association found.

Isolated cerebrospinal fluid hypertension in chronic headache: diagnostic innovations and clinical implications.

Isolated cerebrospinal fluid hypertension (ICH) is a condition of increased cerebrospinal fluid (CSF) pressure in the cranial-spinal compartment without an identifiable cause. Isolated headache is the most common symptom of ICH, while missing may be signs such as papilledema or sixth nerve palsy. This fact makes difficult the clinical diagnosis of headache attributable to ICH in headache sufferers. Another source of confusion stems from the CSF pressure measurement. It has been observed that a single-spot CSF opening pressure measurement may be insufficient to identify elevated CSF pressure in headache sufferers. A new method of CSF pressure measurement has been able to identify pressure-related features of isolated CSF hypertension (ICH). In fact, nocturnal or postural headache and abnormal pressure pulsations are the more common pressure-related features of ICH in patients with chronic headache. The compressive action of these abnormal pressure pulsations causes the periventricular white matter microstructure alterations leading to the focal diffusion tensor imaging findings in patients with ICH. Abnormal pressure pulsations are a marker of ICH in chronic headache. The identification of the CSF pressure-related features may be useful for differentiating headache sufferers with ICH from those with primary headache disorder in clinical practice. The therapeutic strategy in these headache sufferers with ICH includes the CSF removal and a medical treatment.

Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-ß1-42 and Hypertension.

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults. OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations. METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aß1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess WM macro- and microstructural properties. Linear regression analyses were used to assess the relationships among WM alterations, cerebrovascular disease risk, and AD pathology. Voxelwise analyses were performed to examine spatial patterns of WM alteration associated with each pathology. RESULTS: HTN and CSF Aß1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aß1-42 levels were associated with alterations in normal appearing white matter fractional anisotropy (NAWM-FA), whereas HTN was marginally associated with alterations in NAWM-FA. Linear regression analyses demonstrated significant main effects of HTN and CSF Aß1-42 on WMH volume, but no significant HTN×CSF Aß1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aß1-42. CONCLUSION: Associations of HTN and lower CSF Aß1-42 with WM alteration were statistically and spatially distinct, suggesting independent rather than synergistic effects. Considering such spatial distributions may improve diagnostic accuracy to address each underlying pathology.

Human subarachnoid space width oscillations in the resting state.

Abnormal cerebrospinal fluid (CSF) pulsatility has been implicated in patients suffering from various diseases, including multiple sclerosis and hypertension. CSF pulsatility results in subarachnoid space (SAS) width changes, which can be measured with near-infrared transillumination backscattering sounding (NIR-T/BSS). The aim of this study was to combine NIR-T/BSS and wavelet analysis methods to characterise the dynamics of the SAS width within a wide range of frequencies from 0.005 to 2 Hz, with low frequencies studied in detail for the first time. From recordings in the resting state, we also demonstrate the relationships between SAS width in both hemispheres of the brain, and investigate how the SAS width dynamics is related to the blood pressure (BP). These investigations also revealed influences of age and SAS correlation on the dynamics of SAS width and its similarity with the BP. Combination of NIR-T/BSS and time-frequency analysis may open up new frontiers in the understanding and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

Chronic high-sodium diet intake after weaning lead to neurogenic hypertension in adult Wistar rats.

In this study, we investigated some mechanisms involved in sodium-dependent hypertension of rats exposed to chronic salt (NaCl) intake from weaning until adult age. Weaned male Wistar rats were placed under high (0.90% w/w, HS) or regular (0.27% w/w, Cont) sodium diets for 12 weeks. Water consumption, urine output and sodium excretion were higher in HS rats compared to control. Blood pressure (BP) was directly measured by the arterial catheter and found 13.8% higher in HS vs Cont rats. Ganglionic blockade with hexamethonium caused greater fall in the BP of HS rats (33%), and central antagonism of AT1 receptors (losartan) microinjected into the lateral ventricle reduced BP level of HS, but not of Cont group. Heart rate variability analysis revealed sympathetic prevalence on modulation of the systolic interval. HS diet did not affect creatinine clearance. Kidney histological analysis revealed no significant change in renal corpuscle structure. Sodium and potassium concentrations in CSF were found higher in HS rats despite no change in plasma concentration of these ions. Taken together, data suggest that animals exposed to chronic salt intake to a level close to that reported for human' diet since weaning lead to hypertension, which appears to rely on sodium-driven neurogenic mechanisms.

Determining the Enzymatic Activity of Angiotensin-Converting Enzyme 2 (ACE2) in Brain Tissue and Cerebrospinal Fluid Using a Quenched Fluorescent Substrate.

Angiotensin-converting enzyme 2 (ACE2) is a component of the renin-angiotensin system (RAS) which plays an important role in the regulation of blood pressure and volume homeostasis. Accumulating evidence shows alterations in ACE2 expression and activity in several hypertensive animal models, as well as in patients with hypertension. In order to assess the role of brain ACE2 in hypertension, a specific ACE2 assay is required. Based on a quenched fluorescent substrate, we describe an easy-to-use method for determining ACE2 activity in brain tissue and cerebrospinal fluid. The method can further be adapted for other tissues, plasma, cell extracts, and cell culture supernatants.

Retinal vessel diameter and estimated cerebrospinal fluid pressure in arterial hypertension: the Beijing Eye Study.

BACKGROUND: Hypertensive retinal microvascular abnormalities include an increased retinal vein-to-artery diameter ratio. Because central retinal vein pressure depends on cerebrospinal fluid pressure (CSFP), we examined whether the retinal vein-to-artery diameter ratio and other retinal hypertensive signs are associated with CSFP. METHODS: Participants of the population-based Beijing Eye Study (n = 1,574 subjects) underwent measurement of the temporal inferior and superior retinal artery and vein diameter. CSFP was calculated as 0.44 × body mass index (kg/m(2)) + 0.16 × diastolic blood pressure (mm Hg) - 0.18 × age (years) - 1.91. RESULTS: Larger retinal vein diameters and higher vein-to-artery diameter ratios were significantly associated with higher estimated CSFP (P = 0.001) in multivariable analysis. In contrast, temporal inferior retinal arterial diameter was marginally associated (P = 0.03) with estimated CSFP, and temporal superior artery diameter was not significantly associated (P = 0.10) with estimated CSFP; other microvascular abnormalities, such as arteriovenous crossing signs, were also not significantly associated with estimated CSFP. In a reverse manner, higher estimated CSFP as a dependent variable in the multivariable analysis was associated with wider retinal veins and higher vein-to-artery diameter ratio. In the same model, estimated CSFP was not significantly correlated with retinal artery diameters or other retinal microvascular abnormalities. Correspondingly, arterial hypertension was associated with retinal microvascular abnormalities such as arteriovenous crossing signs (P = 0.003), thinner temporal retinal arteries (P < 0.001), higher CSFP (P < 0.001), and wider retinal veins (P = 0.001) or, as a corollary, with a higher vein-to-artery diameter ratio in multivariable analysis. CONCLUSIONS: Wider retinal vein diameters are associated with higher estimated CSFP and vice versa. In arterial hypertension, an increased retinal vein-to-artery diameter ratio depends on elevated CSFP, which is correlated with blood pressure.

Alzheimer's disease markers, hypertension, and gray matter damage in normal elderly.

It is not well known whether Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are associated with brain damage in cognitively normal elderly. The combined influence of CSF biomarkers and hypertension (HTN) on the gray matter (GM) is also not well described. One hundred fifteen cognitively healthy subjects (mean age 62.6 ± 9.5%, 62% women) received clinical assessment, a high resolution magnetic resonance imaging (MRI), and a lumbar puncture. The CSF levels of total tau (t-tau), hyperphosphorylated tau (p-tau(231)), amyloid beta (Aß42/Aß40), p-tau(231)/Aß42, and t-tau/Aß42 were dichotomized as "high" and "low" based on accepted cut off values. Statistical parametric mapping was used to examine MRI scans for regional GM density, studied as a function of the CSF markers, HTN, and combination of both. Global and medial temporal lobe (MTL) GM was also assessed. Voxel based morphometry revealed that higher t-tau was associated with lower GM density in the precunei. Subjects with higher p-tau(231) and p-tau(231)/Aß42 had less GM in temporal lobes. Low Aß42/Aß40 was related to less GM in the thalami, caudate, and midbrain. Subjects with hypertension showed more GM atrophy in the cerebellum, occipital, and frontal regions. Simultaneous presence of elevated CSF AD biomarkers and HTN was associated with more GM atrophy than either marker individually, but no interaction effects were identified. In conclusion, in normal elderly CSF tau markers were associated predominantly with lower GM estimates in structures typically affected early in the AD process. In this presymptomatic stage when no cognitive impairment is present, AD biomarkers and HTN have additive effects on gray matter damage.

Hypertension from chronic central sodium chloride in mice is mediated by the ouabain-binding site on the Na,K-ATPase α2-isoform.

A chronic increase in the concentration of sodium chloride in the cerebrospinal fluid (CSF) (↑CSF [NaCl]) appears to be critically important for the development of salt-dependent hypertension. In agreement with this concept, increasing CSF [NaCl] chronically by intracerebroventricular (icv) infusion of NaCl-rich artificial CSF (aCSF-HiNaCl) in rats produces hypertension by the same mechanisms (i.e., aldosterone-ouabain pathway in the brain) as that produced by dietary sodium in salt-sensitive strains. We first demonstrate here that icv aCSF-HiNaCl for 10 days also causes hypertension in wild-type (WT) mice. We then used both WT and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain-sensitive Na,K-ATPase α(2)-isoform (α2(S/S)), mean arterial pressure rose by ~25 mmHg within 2 days of starting aCSF-HiNaCl (0.6 nmol Na/min) and remained elevated throughout the study. Ouabain (171 pmol/day icv) increased blood pressure to a similar extent. aCSF-HiNaCl or ouabain given at the same rates subcutaneously instead of intracerebroventricularly had no effect on blood pressure. The pressor response to icv aCSF-HiNaCl was abolished by an anti-ouabain antibody given intracerebroventricularly but not subcutaneously, indicating that it is mediated by an endogenous ouabain-like substance in the brain. We compared the effects of icv aCSF-HiNaCl or icv ouabain on blood pressure in α2(S/S) versus knockout/knockin mice with a ouabain-resistant endogenous α(2)-subunit (α2(R/R)). In α2(R/R), there was no pressor response to icv aCSF-HiNaCl in contrast to WT mice. The α2(R/R) genotype also lacked a pressor response to icv ouabain. These data demonstrate that chronic ↑CSF [NaCl] causes hypertension in mice and that the blood pressure response is mediated by the ouabain-like substance in the brain, specifically by its binding to the α(2)-isoform of the Na,K-ATPase.

Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer's disease.

We examined the impact of hypertension on cerebrospinal fluid (CSF) biomarkers amyloid-beta1-42 (Abeta42), total tau (tau), and phosphorylated tau at threonine 181 (ptau-181), and assessed the modifying role of APOE genotype in this relation in 546 patients (mean age 65 +/- 10, 47% female) from our memory-clinic. Of these patients 150 had subjective complaints, 140 were diagnosed with mild cognitive impairment, and 256 with Alzheimer's disease. Linear regression analyses adjusted for age, gender, and diagnosis showed that the association of hypertension with tau and ptau-181 was modified by APOE genotype (p-values for interaction p< 0.05). In APOE epsilon4 homozygotes (n=74), and to a lesser extent in APOE epsilon4 heterozygotes, hypertension was associated with higher tau and ptau-181 levels; beta (95%CI) were 188 (11; 364) pg/mL and 22 (3; 42) pg/mL for the APOE epsilon4 homozygotes. Hypertension was not associated with Abeta42 levels, and APOE genotype did not modify this relation. Our findings suggest that hypertension is directly related to tau pathology in APOE epsilon4 homozygous carriers.

Posterior reversible encephalopathy as the initial manifestation of a Guillain-Barré syndrome.

We report a female patient with posterior reversible encephalopathy syndrome as the initial manifestation of a Guillain-Barré syndrome. She presented with headache and paraesthesias of the fingertips three days after gastroenteritis. Examination revealed hypertension and tachypnoea. Brain MRI showed a bi-occipital vasogenic edema consistent with the syndrome. Subsequent examination showed a tetraparesis. Cerebrospinal fluid analyses revealed albuminocytologic dissociation and the diagnosis of Guillain-Barré syndrome was made. The typical radiological and clinical features of posterior reversible encephalopathy syndrome (headache and hypertension) were present prior to the clinical manifestation of Guillain-Barré syndrome. We suggest posterior reversible encephalopathy syndrome to be considered as an initial manifestation of Guillain-Barré syndrome.

Salt-sensing mechanisms in blood pressure regulation and hypertension.

High salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodeling, cardiac hypertrophy, and stroke incidence. In this review, we discuss the molecular origins of primary sensors involved in the phenomenon of salt sensitivity. Based on the analysis of literature data, we conclude that the kidneys and central nervous system (CNS) are two major sites for salt sensing via several distinct mechanisms: 1) [Cl(-)] sensing in renal tubular fluids, primarily by Na(+)-K(+)-Cl(-) cotransporter (NKCC) isoforms NKCC2B and NKCC2A, whose expression is mainly limited to macula densa cells; 2) [Na(+)] sensing in cerebrospinal fluid (CSF) by a novel isoform of Na(+) channels, Na(x), expressed in subfornical organs; 3) sensing of CSF osmolality by mechanosensitive, nonselective cation channels (transient receptor potential vanilloid type 1 channels), expressed in neuronal cells of supraoptic and paraventricular nuclei; and 4) osmolarity sensing by volume-regulated anion channels in glial cells of supraoptic and paraventricular nuclei. Such multiplicity of salt-sensing mechanisms likely explains the differential effects of Na(+) and Cl(-) loading on the long-term maintenance of elevated blood pressure that is documented in experimental models of salt-sensitive hypertension.

Neuronal responsiveness to central Na+ in 2 congenic strains of Dahl salt-sensitive rats.

Dahl salt-sensitive rats show increased Na(+) entry into the brain on high salt intake and increased sympathetic and pressor responses to central Na(+). We examined C10QTL2 and C17QTL to test whether they contribute to these phenotypes. In Dahl salt-sensitive, Lewis, and C10S.L16, and C17S.L2 congenic rats on a high salt diet for 8 to 10 days, blood pressure and heart rate were higher in Dahl salt-sensitive versus others and in C10S.L16 and C17S.L2 versus Lewis rats. Cerebrospinal fluid [Na(+)] increased by approximately 5 mmol/L in Dahl salt-sensitive, C10S.L16, and C17S.L2 compared with Lewis rats. In rats on a regular salt diet, 8-minute intracerebroventricular infusions of artificial cerebrospinal fluid with increasing [Na(+)] caused increases in blood pressure, heart rate, and renal sympathetic nerve activity, which were approximately 90% larger in Dahl salt-sensitive and C17S.L2 versus Lewis rats and only 35% to 45% larger in C10S.L16 versus Lewis rats. In another set of rats on regular salt, blood pressure and heart rate were recorded by telemetry before and during intracerebroventricular infusion of Na(+)-rich cerebrospinal fluid for 14 days. Na(+)-rich cerebrospinal fluid caused significantly larger increases in blood pressure and heart rate, larger responses to air stress and more impairment of baroreflex in Dahl salt-sensitive and C17S.L2 rats versus Lewis rats. In contrast, responses in C10S.L16 rats were similar to those in Lewis rats. These data suggest that, in Dahl salt-sensitive rats, genetic variants in C10QTL2 but not C17QTL contribute to increased neuronal responsiveness to cerebrospinal fluid [Na(+)]. However, neither of them contributes to the increase in cerebrospinal fluid [Na(+)] induced by high salt.

Hippocampal volume and cognitive performance in long-standing Type 1 diabetic patients without macrovascular complications.

AIMS: Hippocampal atrophy and memory deficits have been reported in Type 2 diabetes. Whether similar alterations occur in Type 1 diabetes is currently unknown. METHODS: In a case-control design, 13 Type 1 diabetic patients with at least 10 years' duration of disease, but free from clinical signs of macrovascular disease, were compared with age- and gender-matched control subjects. Hippocampal volume and measures of global cerebral cerebrospinal fluid (CSF) were determined from magnetic resonance imaging (MRI) scans. Cognitive functions were assessed using four neuropsychological tests. Mood and depression were measured by questionnaires. RESULTS: Hippocampal volume and memory did not differ between Type 1 diabetic patients and control subjects. However, a significantly increased amount of cerebral CSF suggestive of mild cerebral atrophy was observed in the patients. In addition, deficits in psychomotor speed and selective attention were apparent. Eleven of 13 patients had retinopathy and/or nephropathy. Findings were unrelated to cerebrovascular disease, white matter disease or silent strokes. CONCLUSIONS: Results from our small study in Type 1 diabetic patients do not support findings from previous studies of Type 2 diabetic patients demonstrating reductions in hippocampal volume and impaired memory. On the contrary, we observed evidence for mild cerebral atrophy and impaired psychomotor speed and selective attention. This is in line with some previous studies in Type 1 diabetes. If replicated in larger studies, our findings would support the idea that the effects on brain function and structure differ between Type 1 and Type 2 diabetes.

Alterations of the cerebrospinal fluid proteins and subcommissural organ secretion in the arterial hypertension and ventricular dilatation. A study in SHR rats.

The aim of this work was to analyze the proteins in the cerebrospinal fluid (CSF) of spontaneously hypertensive rats, to study their possible role in the relationship between hydrocephalus, arterial hypertension and alterations in the subcommissural organ. Brains from control Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) sacrificed with chloral hydrate were used. Antiserums against some cerebrospinal fluid protein bands and Reissner's fiber (RF) were used for immunohistochemical study of the SCO. Ventricular dilation was observed in the lateral and third ventricle of the SHR. Third ventricle ependyma showed immunoreactive material (IRM) for antibody against 141 kDa protein band anti-B1 and 117 protein band anti-B2 and the SCO of the SHR showed a decrease of the IRM when compared with WKY rats. An alteration in the expression of anti-RF was found to compare the SCO of the WKY and SHR groups. Our results demonstrate that hydrocephalus and hypertension are interconnected in this kind of rat which produce alterations in SCO secretions and some proteins of the CSF.

A comparison of cerebrospinal fluid and plasma urotensin II concentrations in normotensive and hypertensive patients undergoing urological surgery during spinal anesthesia: a pilot study.

UNLABELLED: Urotensin II is a novel endogenous vasoconstrictor. There are no data describing cerebrospinal fluid (CSF) concentrations in humans. Therefore, in this study, we aimed to quantify and compare plasma and CSF urotensin II concentrations in patients with essential hypertension and matched controls. Twenty male patients (10 receiving >6 mo of treatment for essential hypertension and 10 normotensive controls scheduled to undergo urological surgery under spinal anesthesia) were recruited into this single-blinded cohort study. Plasma and CSF urotensin II concentrations were measured by radioimmunoassay, along with mean arterial blood pressure (MAP), before admission, on the day of admission, and immediately before anesthesia. CSF and plasma urotensin II concentrations were low. Median (range) values in CSF for all 20 patients were significantly lower than plasma by approximately 15% (19.0 pg/mL [10.6-24.9 pg/mL] compared with 22.3 pg/mL [17.7-28.4 pg/mL]; P = 0.004). There were no significant differences between normotensive and hypertensive patients in either CSF or plasma concentrations. However, there was a significant positive correlation between average MAP and CSF urotensin II concentrations (r(2) = 0.44; P = 0.036) in the hypertensive group. IMPLICATIONS: Urotensin II is the most potent known endogenous human vasoconstrictor. In this pilot study, we report for the first time that cerebrospinal fluid levels are smaller than plasma levels and that there may be some association with increased blood pressure.

Abnormal spinal fluid in hypertensive encephalopathy.

A 44-year-old white male presented with marked hypertension and encephalopathy. His spinal fluid showed a neutrophilic pleocytosis in the absence of infection. While cases of hypertensive encephalopathy with concomitant minor lymphocytic pleocytosis have been occasionally described, it is distinctly abnormal to have a neutrophilic pleocytosis in this setting.