In euryhaline fish, prolactin (Prl) plays an essential role in freshwater (FW) acclimation. In the euryhaline and eurythermal Mozambique tilapia, Oreochromis mossambicus, Prl cells are model ...osmoreceptors, recently described to be thermosensitive. To investigate the effects of temperature on osmoreception, we incubated Prl cells of tilapia acclimated to either FW or seawater (SW) in different combinations of temperatures (20, 26 and 32 °C) and osmolalities (280, 330 and 420 mOsm/kg) for 6 h. Release of both Prl isoforms, Prl
and Prl
, increased in hyposmotic media and were further augmented with a rise in temperature. Hyposmotically-induced release of Prl
, but not Prl
, was suppressed at 20 °C. In SW fish, mRNA expression of prl
increased with rising temperatures at lower osmolalities, while and prl
decreased at 32 °C and higher osmolalities. In Prl cells of SW-acclimated tilapia incubated in hyperosmotic media, the expressions of Prl receptors, prlr1 and prlr2, and the stretch-activated Ca
channel, trpv4,decreased at 32 °C, suggesting the presence of a cellular mechanism to compensate for elevated Prl release. Transcription factors, pou1f1, pou2f1b, creb3l1, cebpb, stat3, stat1a and nfat1c, known to regulate prl
and prl
, were also downregulated at 32 °C. Our findings provide evidence that osmoreception is modulated by temperature, and that both thermal and osmotic responses vary with acclimation salinity.
Objective
Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought ...to determine whether OAT resumption after ICH is associated with long‐term outcome, accounting for ICH location (ie, lobar vs nonlobar).
Methods
We meta‐analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.‐based single‐center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0–3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models.
Results
We included 1,012 OAT‐related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio HR = 0.25, 95% confidence interval CI = 0.14–0.44, p < 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57–6.94, p < 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17–0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48–6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all‐cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01).
Interpretation
These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755–765
Population-based studies have estimated that about 15% of ischemic strokes are caused by large-vessel cerebrovascular disease. We determined the types of large-vessel atherosclerosis responsible for ...ischemic strokes in a population-based stroke study.
Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated, and age-, race- and sex-adjusted to the 2000 US population.
There were 2,204 ischemic strokes, including 365 strokes of large-vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery (ICA) stenosis was associated with 8.0% of all ischemic strokes, while extracranial ICA occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial ICA was 13.4 (11.4-15.4) per 100,000 persons. We conservatively estimate that about 41,000 strokes may be attributed to extracranial ICA stenosis annually in the United States.
Large-vessel atherosclerosis is an important cause of stroke, with extracranial ICA stenosis being significantly more common than extracranial ICA occlusion or intracranial atherosclerotic disease.
OBJECTIVETo test the hypothesis that patients with deep intracerebral hemorrhage (ICH) would encounter hematoma expansion (HE) more frequently compared to lobar ICH patients.
METHODSICH patients with ...neuroimaging to calculate HE were analyzed from the multicenter ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) cohort. Patients with laboratory coagulopathy or preceding anticoagulant use were excluded to assess relationships of ICH location alone (deep vs lobar) with HE, defined as >33% relative growth. Odds ratios (OR) and 95% confidence intervals (CI) for these relationships were estimated using logistic regression. Sensitivity and specificity determined HE thresholds best associated with poor 3-month outcomes (modified Rankin 4-6) stratified by location.
RESULTSThere were 1,049 deep and 408 lobar ICH patients analyzed. Deep ICH locations were more likely to have HE (adjusted OR 1.57, 95% CI 1.08–2.29) after adjusting for age, sex, race, baseline hematoma size, and intraventricular hemorrhage. However, this difference was non-significant (adjusted OR 1.35, 95% CI 0.81–2.24) after controlling for time from symptom onset to admission CT in a subgroup analysis of 729 patients with this data. Yet, the threshold of HE best associated with poor outcomes was smaller in deep (30%) compared to lobar (50%) ICH.
CONCLUSIONSWhile HE was more frequent in deep than lobar ICH, this could be due to differences in symptom onset to admission CT times in our cohort. However, deep ICH patients appear particularly vulnerable to the deleterious effects of small volumes of HE. Further studies should clarify whether ICH location needs to be considered in HE treatment paradigms.
Little is known about the distribution of National Institutes of Health Stroke Scale (NIHSS) scores from patients with ischemic stroke sampled from population-based studies. We describe the ...distribution of NIHSS in ischemic stroke cases from the Cincinnati/Northern Kentucky Stroke Study.
Within a biracial population of 1.3 million, all strokes among area residents in 2005 were ascertained by screening discharge records at local hospitals and outpatient clinics. A sampling scheme was developed to ascertain additional cases presenting to physician offices and nursing homes, not identified through the other sources. All confirmed ischemic stroke cases underwent chart abstraction, and a retrospective NIHSS (rNIHSS) score (range, 0-42) was generated on the basis of initial physician examination findings.
There were 2233 ischemic stroke cases identified during the 12-month study. The overall median rNIHSS score was 3 (interquartile range, 1-7). Median rNIHSS score was 3, 7, and 1, respectively, for stroke cases ascertained through the admitted, in-hospital, and out-of-hospital sources. Median rNIHSS was significantly higher in subjects ≥80 years compared with younger cases (4 versus 3).
More than half of all ischemic stroke cases have mild symptom severity on initial presentation (ie, rNIHSS≤3). Monitoring trends in NIHSS represents a legitimate target for population-based surveillance efforts.
Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension ...management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 MTAG P-value (P) = 2.6 × 10-8 at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS.
Tilapia prolactin cells are thermosensitive osmoreceptors Woo, Daniel W; Malintha, G H T; Celino-Brady, Fritzie T ...
American journal of physiology. Regulatory, integrative and comparative physiology,
06/2022, Letnik:
322, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Prolactin (PRL) cells within the
(RPD) of euryhaline and eurythermal Mozambique tilapia,
, rapidly respond to a hyposmotic stimulus by releasing two distinct PRL isoforms, PRL
and PRL
. Here, we ...describe how environmentally relevant temperature changes affected mRNA levels of
and
and the release of immunoreactive prolactins from RPDs and dispersed PRL cells. When applied under isosmotic conditions (330 mosmol/kgH
O), a 6°C rise in temperature stimulated the release of PRL
and PRL
from both RPDs and dispersed PRL cells under perifusion. When exposed to this same change in temperature, ∼50% of dispersed PRL cells gradually increased in volume by ∼8%, a response partially inhibited by the water channel blocker, mercuric chloride. Following their response to increased temperature, PRL cells remained responsive to a hyposmotic stimulus (280 mosmol/kgH
O). The mRNA expression of
, a Ca
-channel involved in hyposmotically induced PRL release, was elevated in response to a rise in temperature in dispersed PRL cells and RPDs at 6 and 24 h, respectively;
and
mRNAs were unaffected. Our findings indicate that thermosensitive PRL release is mediated, at least partially, through a cell-volume-dependent pathway similar to how osmoreceptive PRL release is achieved.
OBJECTIVE:To characterize temporal trends in subarachnoid hemorrhage (SAH) incidence and outcomes over 5 time periods in a large population-based stroke study in the United States.
METHODS:All SAHs ...among residents of the Greater Cincinnati/Northern Kentucky region at least 20 years of age were identified and verified via study physician review in 5 distinct year-long study periods between 1988 and 2010. We abstracted demographics, care patterns, and outcomes, and we compared incidence and case-fatality rates across the study periods.
RESULTS:The incidence of SAH in the 5 study periods (age-, race-, and sex-adjusted to the 2000 US population) was 8.8 (95% confidence interval 6.8–10.7), 9.2 (7.2–11.2), 10.0 (8.0–12.0), 9.0 (7.1–10.9), and 7.7 (6.0–9.4) per 100,000, respectively; the trend in incidence rates from 1988 to 2010 was not statistically significant (p = 0.22). Advanced neurovascular imaging, endovascular coiling, and neurologic intensive care unit availability increased significantly over time. All-cause 5-day (32%–18%, p = 0.01; for trend), 30-day (46%–25%, p = 0.001), and 90-day (49%–29%, p = 0.001) case-fatality rates declined from 1988 to 2010. When we included only proven or highly likely aneurysmal SAH, the declines in case-fatality were no longer statistically significant.
CONCLUSIONS:Although the incidence of SAH remained stable in this population-based region, 5-day, 30-day, and 90-day case-fatality rates declined significantly. Advances in surgical and medical management, along with systems-based changes such as the emergence of neurocritical care units, are potential explanations for the reduced case-fatality.
Background:
Cognitive impairment (CI) is commonly observed after intracerebral hemorrhage (ICH). While a growing number of studies have explored this association, several evidence gaps persist. This ...review seeks to investigate the relationship between CI and ICH.
Methods:
A two-stage systematic review of research articles, clinical trials, and case series was performed. Initial search used the keywords “Intracerebral hemorrhage” OR “ICH” AND “Cognitive Impairment” OR “Dementia OR “Cognitive Decline” within the PubMed (last accessed November 3rd, 2020) and ScienceDirect (last accessed October 27th, 2020) databases, without publication date limits. Articles that addressed CI and spontaneous ICH were accepted if CI was assessed after ICH. Articles were rejected if they did not independently address an adult human population or spontaneous ICH, didn't link CI to ICH, were an unrelated document type, or were not written in English. A secondary snowball literature search was performed using reviews identified by the initial search. The Agency for Healthcare research and Quality's assessment tool was used to evaluate bias within studies. Rates of CI and contributory factors were investigated.
Results:
Search yielded 32 articles that collectively included 22,631 patients. Present evidence indicates a high rate of post-ICH CI (65–84%) in the acute phase (<4 weeks) which is relatively lower at 3 (17.3–40.2%) and 6 months (19–63.3%). Longer term follow-up (≥1 year) demonstrates a gradual increase in CI. Advanced age, female sex, and prior stroke were associated with higher rates of CI. Associations between post-ICH CI and cerebral microbleeds, superficial siderosis, and ICH volume also exist. Pre-ICH cognitive assessment was missing in 28% of included studies. The Mini Mental State Evaluation (44%) and Montreal Cognitive Assessment (16%) were the most common cognitive assessments, albeit with variable thresholds and definitions. Studies rarely (<10%) addressed racial and ethnic disparities.
Discussion:
Current findings suggest a dynamic course of post-ICH cognitive impairment that may depend on genetic, sociodemographic and clinical factors. Methodological heterogeneity prevented meta-analysis, limiting results. There is a need for the methodologies and time points of post-ICH cognitive assessments to be harmonized across diverse clinical and demographic populations.
The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral ...hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure-lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).
We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography (<6 hours of intracerebral hemorrhage onset) by 3 independent neurologists blind to clinical data.
WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02-1.98), 1.47 (1.08-1.99), and 1.64 (1.21-2.22), respectively (all P for trend <0.05). There was no association between lacunes and outcomes. There were no significant differences in the effects of intensive blood pressure-lowering across subgroups of cerebral SVD.
Preexisting cerebral SVD manifestations of WML and brain atrophy predict poor outcome in acute intracerebral hemorrhage. There is no apparent hazard of early intensive lowering of blood pressure according to the INTERACT2 protocol, in patients with underlying cerebral SVD.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.
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