- The spatial cerebral damage caused by larger infarct and β-amyloid toxicity is driven by the anatomical/functional connectivity. [Journal Article]
- JCJ Comp Neurol 2019 Jul 02
- Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce.…
Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce. It remains to be determined if the co-morbid concurrence of large infarct and β-amyloid (Aβ) toxicity can precipitate the early development of dementia. Here, we described a dose-dependent effect of a unilateral striatal injection of vasoconstrictive endothelin-1 (ET-1) along with Aβ toxicity on CNS pathogenesis; driven by the anatomical and functional networks within a brain circuit. After 21 days of treatment, a high dose (60 pmol) of ET-1 (E60) alone caused the greatest increase in neuroinflammation, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion such as white matter (sub-cortical white matter, corpus callosum, internal capsule, anterior commissure), gray matter (globus pallidus, thalamus) and cortices (cingulate, motor, somatosensory, entorhinal). The combined E60 + Aβ treatment also extended perturbation in the contralateral hemisphere of these rats, such as increased deposition of amyloid precursor protein fragments associated with the appearance of degenerating cells and the leakage of laminin from the basement membrane across a compromised blood-brain barrier. However, the cerebral damage induced by the 6 pmol ET-1 (E6), Aβ and E6 + Aβ rats was not detrimental enough to injure the complete network. The appreciation of the causal interactions among distinct anatomical units in the brain after ischemia and Aβ toxicity will help in the design of effective and alternative therapeutics that may disassociate the synergistic or additive association between the infarcts and Aβ toxicity. This article is protected by copyright. All rights reserved.
- Pseudohypoadrenocorticism in a Siberian Husky with Trichuris vulpis Infection. [Case Reports]
- CRCase Rep Vet Med 2019; 2019:3759683
- An entire male Siberian Husky presented for diarrhoea, weakness, inappetence, and collapse following a six-day period of illness. On clinical examination the dog displayed vasoconstrictive circulator…
An entire male Siberian Husky presented for diarrhoea, weakness, inappetence, and collapse following a six-day period of illness. On clinical examination the dog displayed vasoconstrictive circulatory shock, dehydration, and melena. Laboratory tests revealed a marked hyponatraemia, hyperkalaemia, and a decreased sodium/potassium ratio of ≤ 12.4. The baseline and poststimulation serum cortisol concentrations were markedly elevated following adrenocorticotropin hormone (ACTH) stimulation test, yielding 712 nmol/L and 706 nmol/L, respectively. The elevated cortisol concentration excluded hypoadrenocorticism. A concurrent Trichuris vulpis (whipworm) infection was also identified. The dog was treated with supportive care including fenbendazole and recovered uneventfully. The final diagnosis was Trichuris vulpis infection with secondary pseudohypoadrenocorticism. This case report further supports a previous observation that the Siberian Husky breed may have an increased sensitivity to infection with Trichuris vulpis and development of pseudohypoadrenocorticism.
- Dysregulation of the placental renin-angiotensin system in human fetal growth restriction. [Journal Article]
- RReproduction 2019 Jun 01
- Fetal growth restriction (FGR) is a pregnancy complication wherein the fetus fails to reach its growth potential. The renin-angiotensin system (RAS) is a critical regulator of placental function, con…
Fetal growth restriction (FGR) is a pregnancy complication wherein the fetus fails to reach its growth potential. The renin-angiotensin system (RAS) is a critical regulator of placental function, controlling trophoblast proliferation, angiogenesis and blood flow. The RAS significantly influences uteroplacental blood flow through the balance of its vasoconstrictive and vasodilatory pathways. Although the RAS is known to be dysregulated in placentae from women with preeclampsia, the expression of the RAS has not yet been studied in pregnancies compromised by FGR alone. This study investigated the mRNA expression and protein levels of RAS components in placentae from pregnancies compromised by FGR. Angiotensin II type 1 receptor (AGTR1) and angiotensin-converting enzyme 2 (ACE2) mRNA levels were reduced in FGR placentae compared with control (P=0.012 and 0.018 respectively). Neprilysin (NEP) mRNA expression was lower in FGR placentae compared with control (P=0.004). MRNA levels of angiotensinogen (AGT) tended to be higher in FGR placentae compared with control (P=0.090). Expression of prorenin, AGT, angiotensin converting enzyme (ACE) or ACE2 proteins were similar in control and FGR placentae. The renin-AGT reaction is a first order reaction so levels of expression of placental AGT determine levels of Ang II. Decreasing levels of ACE2 and/or NEP by limiting the production of Ang-(1-7), which is a vasodilator, and increasing placental Ang II levels (vasoconstrictor) may result in an imbalance between the vasoconstrictor and vasodilator arms of the placental RAS. Ultimately this dysregulation of the placental RAS could lead to reduced placental perfusion that is evident in FGR.
- Transvascular Pacing of Aorticorenal Ganglia Provides a Testable Procedural Endpoint for Renal Artery Denervation. [Journal Article]
- JCJACC Cardiovasc Interv 2019 Jun 24; 12(12):1109-1120
- CONCLUSIONS: Transvascular ARG pace-capture is feasible and recognized by concurrent hypertensive and ipsilateral renal arterial vasoconstrictive responses. Abolition of ARG pacing-induced vasoconstriction may indicate successful renal sympathetic denervation and serve as a physiological procedural endpoint to guide transcatheter renal denervation.
- A randomized comparison of the coronary vasomotor function and myocardial flow in patients treated with everolimus-eluting bioresorbable scaffolds and everolimus-eluting metallic stents. [Journal Article]
- EEuroIntervention 2019 06 18
- CONCLUSIONS: BVS and EES had similar microcirculatory response to hyperemia and predominant vasoconstrictive response in the peri-scaffold segments to endothelial-dependent stimuli. However, BVS exhibited larger vasoconstriction to endothelial-dependent stimuli in the scaffold segment.
- Dopamine enhancement of dextrorphan-induced skin antinociception in response to needle pinpricks in rats. [Journal Article]
- PRPharmacol Rep 2019 Apr 20; 71(4):732-737
- CONCLUSIONS: When compared to dopamine, dextrorphan was more potent and had a shorter duration of skin nociceptive block. Dopamine produced a synergistic effect on dextrorphan-mediated antinociception, and prolonged dextrorphan's antinociceptive duration.
- Hypocapnia after traumatic brain injury: how does it affect the time constant of the cerebral circulation? [Journal Article]
- JCJ Clin Monit Comput 2019 Jun 07
- The time constant of the cerebral arterial bed ("tau") estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor-capacitor circuit, it is…
The time constant of the cerebral arterial bed ("tau") estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor-capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO2 reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm3/s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance.
- Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo-continuous arterial spin labeling. [Journal Article]
- NBNMR Biomed 2019; 32(8):e4105
- Arterial spin labeling (ASL)-MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disea…
Arterial spin labeling (ASL)-MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disease are frequently used in translational MRI studies, which are commonly performed under anesthesia. Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. Isoflurane is a frequently used anesthetic with vasodilative properties. Here, the influence of three distinct isoflurane protocols was studied with pseudo-continuous ASL in two different mouse strains. The first protocol was a free-breathing set-up with medium concentrations, the second a free-breathing set-up with low induction and maintenance concentrations, and the third a set-up with medium concentrations and mechanical ventilation. A protocol with the vasoconstrictive anesthetic medetomidine was used as a comparison. As expected, medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole-brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole-brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). Furthermore, CVR was shown to be dependent on baseline CBF, regardless of the anesthesia protocol used.
- Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN. [Journal Article]
- CCephalalgia 2019; 39(8):957-966
- CONCLUSIONS: As a centrally-penetrant drug, lasmiditan use was associated with neurologic treatment-emergent adverse events; most were mild or moderate in severity and self-limiting.
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- Chronic Kidney Disease and Pregnancy. [Journal Article]
- OGObstet Gynecol 2019; 133(6):1182-1194
- Chronic kidney disease represents a heterogeneous group of disorders characterized by alterations in the structure and function of the kidney. Chronic kidney disease significantly increases the risk …
Chronic kidney disease represents a heterogeneous group of disorders characterized by alterations in the structure and function of the kidney. Chronic kidney disease significantly increases the risk of adverse maternal and perinatal outcomes, and these risks increase with the severity of the underlying renal dysfunction, degree of proteinuria, as well as the frequent coexistence of hypertension. Further, renal anatomic changes result in dilatation of the collecting system, and physiologic adaptations include alterations in the balance of vasodilatory and vasoconstrictive hormones, resulting in decreased systemic and renal vascular resistance, increased glomerular filtration rate, and modifications in tubular function. These alterations have important clinical implications and can make the diagnosis of renal compromise challenging. The effect of pregnancy on kidney disease may manifest as a loss of renal function, particularly in the context of concomitant hypertension and proteinuria, and chronic kidney disease, even when mild, contributes to the high risk of adverse pregnancy outcomes, including increased risks of preeclampsia, preterm delivery, and small-for-gestational age neonates. Strategies for optimization of pregnancy outcomes include meticulous management of hypertension and proteinuria where possible and the initiation of preeclampsia prevention strategies, including aspirin. Avoidance of nephrotoxic and teratogenic medications is necessary, and renal dosing of commonly used medications must also be considered. Mode of delivery in women with chronic kidney disease should be based on usual obstetric indications, although more frequent prenatal assessments by an expert multidisciplinary team are desirable for the care of this particularly vulnerable patient population. Obstetricians represent a critical component of this team responsible for managing each stage of pregnancy to optimize both maternal and neonatal outcomes, but collaboration with nephrology colleagues in combined clinics wherein both specialists can make joint management decisions is typically very helpful.