Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how

2021 ◽  
Author(s):  
Yan Wang ◽  
Fuzheng Guo
1987 ◽  
Vol 62 (4) ◽  
pp. 1582-1588 ◽  
Author(s):  
S. Javaheri

We hypothesized that inhibition of carbonic anhydrase in the central nervous system by acetazolamide should limit the rise in cisternal cerebrospinal fluid (CSF) [HCO3-] observed in metabolic alkalosis. To test this hypothesis, isosmotic isonatremic metabolic alkalosis was produced in two groups of anesthetized, paralyzed, and mechanically ventilated dogs (8 in each group). Group II animals received 50 mg/kg of acetazolamide intravenously 1 h before induction of metabolic alkalosis of 5-h duration. Renal effects of acetazolamide were eliminated by ligation of renal pedicles. In both groups cisternal CSF [Na+] remained relatively constant during metabolic alkalosis. In group I CSF [Cl-] decreased 3.6 and 8.2 meq/l, respectively, 2.5 and 5 h after induction of metabolic alkalosis. Respective increments in CSF [HCO3-] were 3.4 and 6.0 meq/l. In acetazolamide-treated dogs, during metabolic alkalosis, increments in CSF [HCO3-] (4.8 and 7.2 meq/l, respectively, at 2.5 and 5 h) and decrements in CSF [Cl-] (9.1 and 13.3 meq/l) were greater than those observed in group I. We conclude that, in dogs with metabolic alkalosis and bilateral ligation of renal pedicles, acetazolamide impairs CSF regulation of HCO3- and Cl- ions; acetazolamide not only failed to impede HCO3- rise but actually appeared to increase it. The mechanisms for these observations are discussed.


2020 ◽  
Vol 13 ◽  
Author(s):  
Karolina Serwach ◽  
Joanna Gruszczynska-Biegala

Stromal interaction molecules (STIMs), including STIM1 and STIM2, are single-pass transmembrane proteins that are located predominantly in the endoplasmic reticulum (ER). They serve as calcium ion (Ca2+) sensors within the ER. In the central nervous system (CNS), they are involved mainly in Orai-mediated store-operated Ca2+ entry (SOCE). The key molecular components of the SOCE pathway are well-characterized, but the molecular mechanisms that underlie the regulation of this pathway need further investigation. Numerous intracellular target proteins that are located in the plasma membrane, ER, cytoskeleton, and cytoplasm have been reported to play essential roles in concert with STIMs, such as conformational changes in STIMs, their translocation, the stabilization of their interactions with Orai, and the activation of other channels. The present review focuses on numerous regulators, such as Homer, SOCE-associated regulatory factor (SARAF), septin, synaptopodin, golli proteins, partner of STIM1 (POST), and transcription factors and proteasome inhibitors that regulate STIM-Orai interactions in the CNS. Further we describe novel roles of STIMs in mediating Ca2+ influx via other than Orai pathways, including TRPC channels, VGCCs, AMPA and NMDA receptors, and group I metabotropic glutamate receptors. This review also summarizes recent findings on additional molecular targets of STIM proteins including SERCA, IP3Rs, end-binding proteins (EB), presenilin, and CaMKII. Dysregulation of the SOCE-associated toolkit, including STIMs, contributes to the development of neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Huntington's disease), traumatic brain injury, epilepsy, and stroke. Emerging evidence points to the role of STIM proteins and several of their molecular effectors and regulators in neuronal and glial physiology and pathology, suggesting their potential application for future therapeutic strategies.


2020 ◽  
Author(s):  
Piotr Czupryna ◽  
Agnieszka Kulczyńka-Przybik ◽  
Barbara Mroczko ◽  
Mulugeta Wondim ◽  
Sambor Grygorczuk ◽  
...  

Abstract Background Tick-Borne Encephalitis (TBE) is a viral infection of the Central Nervous System (CNS) caused by Tick-Borne Encephalitis Virus (TBEV). It might take several clinical courses such as: meningitis, meningoencephalitis or meningoencephalomyelitis. The aim this study was to compare the YKL-40 concentration in cerebrospinal fluid (CSF) of patients with different clinical presentations of TBE and patients with excluded meningitis (control group). Methods The concentration of YKL-40 in CSF was determined using Fujirebio tests (Ghent, Belgium) in 32 patients with TBE: group I—patients with meningoencephalitis (n = 16); group II—patients with meningitis (n = 16). The control group (CG) consisted of 17 patients in whom inflammatory process in central nervous system was excluded. Results The concentration of YKL-40 was significantly higher in encephalitis group than in CG after 7 days from the last dose of treatment. The concentration in patients with neuroinflammation had significantly different concentration of YKL-40 compared to patients with no neuroinflammation control groups. ROC curve analysis indicates that: CSF YKL-40 concentration at cut off 783.87 differentiated TBE patients from CG with 100% specificity and 70% sensitivity and CSF YKL-40 concentration at cut off 980.11 differentiated meningitis from meningoencephalitis with 87.5% specificity and 62.5% sensitivity. Conclusions YKL-40 takes part in TBE pathogenesis, its concentration is the highest at the early stage of Central Nervous System involvement and decreases in the convalescent period. As YKL-40 is significantly higher in meningitis than in meningoencephalitis, it might be used as biomarker in differentiation of these clinical forms of TBE.


Author(s):  
H.O. Soloviova

The adaptation of late premature babies to the new life conditions is difficult and requires careful monitoring of all vital parameters in the postnatal period. The general immaturity of the newborns in combination with the metabolic and hypoxic disorders "leaves only a narrow corridor" to develop babies their compensatory possibilities. There is an urgent need to investigate posthypoxic myocardial ischemia in newborns due to the fact that in the neonatal period, early diagnosis and correct treatment can prevent long-term adverse consequences of existing disorders. The aim of this study was to develop an approach for early detection of cardiac rhythm disturbances and conduction disorders in late premature infants, who underwent perinatal hypoxia. A single-center study included 93 late premature babies who were born at the Perinatal Center, Poltava, in 2019 – 2020. Group I consisted of newborns (n ​​= 47) with hypoxic-ischemic damage of the central nervous system; group II included premature babies (n = 46) with hypoxic-hemorrhagic damage of the central nervous system. Long-term monitoring of the electrocardiogram was performed with further conversion of the altered QRST-QRST complexes into 2D format with a multi-coloured representation of all components of the ventricular electrical systole. Among heterotopic cardiac arrhythmias, supraventricular extrasystoles were most often recorded in 89.4 ± 4.8% of the children of group I and in 67.4 ± 6.1% of newborns in group II with daytime distribution in both groups. Ventricular extrasystoles were found as significantly more frequent in newborns of group I (21.3 ± 6.3%) compared with children in group II (10.9 ± 6.1%), with a significant increase in the area of ​​ectopic ventricular complexes (1492.2) that indicates a prolonged depolarization process. The study of the bioelectrical activity of the heart based on the findings obtained by monitoring the electrocardiogram with the qualitative and quantitative analysis of the convertible QRST-QRST complexes increases the efficiency of visual diagnosis of electrical instability of the myocardium in late premature infants with perinatal damage of the central nervous system.


1948 ◽  
Vol 38 (2) ◽  
pp. 229-241 ◽  
Author(s):  
Hedley R. Marston ◽  
Hector John Lee

SUMMARYThe effects of copper deficiency and of copper excess on mature Merino and Border-Leicester ewes were studied experimentally over a period of 3½ years with five evenly matched groups of each breed which were all depastured together as one flock on terrain where sheep develop cobalt and copper deficiency. All were treated with the equivalent of 1 mg. Co/day. Copper was administered thrice weekly in doses which provided for individuals of the respective groups the equivalent of nil, 1, 5, 50 and 100 mg. Cu/day.All of the individuals that received only cobalt became anaemic; they lost weight and developed marked symptoms of copper deficiency.The supplement of 1 mg. Cu/day was sufficient to delay the onset of these symptoms, but it failed to increase significantly the concentration of copper in the blood and it was insufficient to ensure normal myelin formation in the central nervous system of lambs born of the ewes which had received this treatment for 2 years prior to mating.


1986 ◽  
Vol 61 (2) ◽  
pp. 633-639 ◽  
Author(s):  
S. Javaheri ◽  
J. Kennealy ◽  
C. D. Runck ◽  
R. G. Loudon ◽  
M. B. Pine ◽  
...  

We hypothesized that, during isosmotic isonatremic HCl acidosis with maintained isocapnia in cisternal cerebrospinal fluid (CSF), acetazolamide, by inhibiting carbonic anhydrase (CA) in the central nervous system (CNS), should produce an isonatric hyperchloric metabolic acidosis in CSF. Blood and CSF ions and acid-base variables were measured in two groups of anesthetized and paralyzed dogs with bilateral ligation of renal pedicles during 5 h of HCl acidosis (plasma [HCO3-] = 11 meq/l). Mechanical ventilation was regulated such that arterial PCO2 dropped and CSF Pco2 remained relatively constant. In group I (control group, n = 6), CSF [Na+] remained unchanged, [HCO3-] and strong ions difference (SID) fell, respectively, 6.1 and 5 meq/l, and [Cl-] rose 3.5 meq/l after 5 h of acidosis. In acetazolamide-treated animals, (group II, n = 7), CSF [Na+] remained unchanged, [HCO3-], and SID fell 11 and 7.1 meq/l, respectively, and [Cl-] rose 7.1 meq/l. We conclude that during HCl acidosis inhibition of CNS CA by acetazolamide induces an isonatric hyperchloric metabolic acidosis in CSF, which is more severe than that observed in controls.


PEDIATRICS ◽  
1963 ◽  
Vol 31 (6) ◽  
pp. 1024-1027
Author(s):  
Audrey E. Evans

Fifty lumbar punctures were performed on each of three groups of leukemic children. The three categories studied were (1) those with central nervous system manifestations, (2) those free of symptoms following effective treatment, and (3) those not yet having developed central nervous system symptoms. The patients in Group I all had abnormal cerebrospinal fluid. Those examined before or between episodes referable to the central nervous system had normal findings, with rare exceptions. Positive results in the patients without symptoms almost always indicated the early recurrence of central nervous system symptoms.


2021 ◽  
Author(s):  
Piotr Czupryna ◽  
Agnieszka Kulczyńska-Przybik ◽  
Barbara Mroczko ◽  
Mulugeta Wondim ◽  
Sambor Grygorczuk ◽  
...  

Abstract Background Tick-Borne Encephalitis (TBE) is a viral infection of the Central Nervous System (CNS) caused by Tick-Borne Encephalitis Virus (TBEV). It might take several clinical courses such as: meningitis, meningoencephalitis or meningoencephalomyelitis. The aim this study was to compare the YKL-40 concentration in cerebrospinal fluid (CSF) of patients with different clinical presentations of TBE and patients with excluded meningitis (control group). Methods The concentration of YKL-40 in CSF was determined using Fujirebio tests (Ghent, Belgium) in 32 patients with TBE: group I—patients with meningoencephalitis (n = 16); group II—patients with meningitis (n = 16). The control group (CG) consisted of 17 patients in whom inflammatory process in central nervous system was excluded. Results The concentration of YKL-40 was significantly higher in encephalitis group than in CG after 7 days from the last dose of treatment. The concentration in patients with neuroinflammation had significantly different concentration of YKL-40 compared to patients with no neuroinflammation control groups. ROC curve analysis indicates that: CSF YKL-40 concentration at cut off 783.87 differentiated TBE patients from CG with 100% specificity and 70% sensitivity and CSF YKL-40 concentration at cut off 980.11 differentiated meningitis from meningoencephalitis with 87.5% specificity and 62.5% sensitivity. Conclusions YKL-40 takes part in TBE pathogenesis, its concentration is the highest at the early stage of Central Nervous System involvement and decreases in the convalescent period. As YKL-40 is significantly higher in meningitis than in meningoencephalitis, it might be used as biomarker in differentiation of these clinical forms of TBE.


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