scholarly journals Anaerobic Function of CNS White Matter Declines with Age

2010 ◽  
Vol 31 (4) ◽  
pp. 996-1002 ◽  
Author(s):  
Margaret A Hamner ◽  
Thomas Möller ◽  
Bruce R Ransom
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Optic Nerve ◽  
Brain Injuries ◽  
Energy Levels ◽  
Compound Action Potential ◽  
Clinical Impression ◽  
Old Mice ◽  
Compound Action

The mammalian central nervous system (CNS) is generally believed to be completely dependent on the presence of oxygen (O2) to maintain energy levels necessary for excitability. However, previous studies on CNS white matter (WM) have shown that a large subset of CNS-myelinated axons of mice aged 4 to 6 weeks remains excitable in the absence of O2. We investigated whether this surprising WM tolerance to anoxia varied with age. Acutely isolated mouse optic nerve (MON), a purely myelinated WM tract, was studied electrophysiologically. Excitability in the MONs from 1-month-, 4-month-, and 8-month-old mice was assessed quantitatively as the area under the supramaximal compound action potential (CAP). Anoxia-resistant WM function declined with age. After 60 minutes of anoxia, ∼23% of the CAP remained in 1-month-old mice, 8% in 4-month-old mice, and ∼0 in the 8-month-old group. Our results indicated that although some CNS axons function anaerobically in young adult animals, they lose this ability in later adulthood. This finding may help explain the clinical impression that favorable outcome after stroke and other brain injuries declines with age.

scholarly journals Glioblastoma infiltration into central nervous system tissue in vitro: involvement of a metalloprotease.

1988 ◽  
Vol 107 (6) ◽  
pp. 2281-2291 ◽  
Author(s):  
P A Paganetti ◽  
P Caroni ◽  
M E Schwab
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Optic Nerve ◽  
Cell Attachment ◽  
Neurite Growth ◽  
Cell Spreading ◽  
C6 Cells ◽  
3T3 Fibroblasts

Differentiated oligodendrocytes and central nervous system (CNS) myelin are nonpermissive substrates for neurite growth and for cell attachment and spreading. This property is due to the presence of membrane-bound inhibitory proteins of 35 and 250 kD and is specifically neutralized by monoclonal antibody IN-1 (Caroni, P., and M. E. Schwab. 1988. Neuron. 1:85-96). Using rat optic nerve explants, CNS frozen sections, cultured oligodendrocytes or CNS myelin, we show here that highly invasive CNS tumor line (C6 glioblastoma) was not inhibited by these myelin-associated inhibitory components. Lack of inhibition was due to a specific mechanism as the metalloenzyme blocker 1,10-phenanthroline and two synthetic dipeptides containing metalloprotease-blocking sequences (gly-phe, tyr-tyr) specifically impaired C6 cell spreading on CNS myelin. In the presence of these inhibitors, C6 cells were affected by the IN-1-sensitive inhibitors in the same manner as control cells, e.g., 3T3 fibroblasts or B16 melanomas. Specific blockers of the serine, cysteine, and aspartyl protease classes had no effect. C6 cell spreading on inhibitor-free substrates such as CNS gray matter, peripheral nervous system myelin, glass, or poly-D-lysine was not sensitive to 1,10-phenanthroline. The nonpermissive substrate properties of CNS myelin were strongly reduced by incubation with a plasma membrane fraction prepared from C6 cells. This reduction was sensitive to the same inhibitors of metalloproteases. In our in vitro model for CNS white matter invasion, cell infiltration of optic nerve explants, which occurred with C6 cells but not with 3T3 fibroblasts or B16 melanomas, was impaired by the presence of the metalloprotease blockers. These results suggest that C6 cell infiltrative behavior in CNS white matter in vitro occurs by means of a metalloproteolytic activity, which probably acts on the myelin-associated inhibitory substrates.

scholarly journals TRPA1 block protects against loss of white matter function during ischaemia in the mouse optic nerve

2021 ◽  
Author(s):  
Grace Flower ◽  
Vincenzo Giacco ◽  
Angela Roxas ◽  
Nicola B Hamilton-Whitaker ◽  
Andra Braban
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Neuronal Excitability ◽  
Glucose Deprivation ◽  
Compound Action Potential ◽  
Oxygen And Glucose Deprivation ◽  
Loss And Damage ◽  
Compound Action Potentials ◽  
Compound Action

Oligodendrocytes produce myelin which provides insulation to axons and speeds up neuronal transmission. In ischaemic conditions myelin is damaged, resulting to mental and physical disabilities. Therefore, it is important to understand how the functionality of oligodendrocytes and myelin is affected by ischaemia. Recent evidence suggests that oligodendrocyte damage during ischaemia is mediated by TRPA1, whose activation raises intracellular Ca2+ concentrations and damages compact myelin. Here, we show that TRPA1 is tonically active in oligodendrocytes and the optic nerve, as the specific TRPA1 antagonist, A-967079, decreases basal oligodendrocyte Ca2+ concentrations and increases the size of the compound action potential. Conversely, TRPA1 agonists reduce the size of the optic nerve compound action potential, and this effect is significantly reduced by the TRPA1 antagonist. These results indicate that glial TRPA1 regulates neuronal excitability in the white matter under physiological as well as pathological conditions. Importantly, we find that inhibition of TRPA1 prevents loss of compound action potentials during oxygen and glucose deprivation (OGD) and improves the recovery. TRPA1 block was effective when applied before, during or after OGD, indicating that the damage is occurring during ischaemia, but that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain, and that its block may be effective in treating oligodendrocyte loss and damage in many white matter diseases.

scholarly journals Anoxia-Induced Changes in Extracellular K+ and pH in Mammalian Central White Matter

1992 ◽  
Vol 12 (4) ◽  
pp. 593-602 ◽  
Author(s):  
Bruce R. Ransom ◽  
Wolfgang Walz ◽  
Peter K. Davis ◽  
Walter G. Carlini
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Glucose Concentration ◽  
Anaerobic Metabolism ◽  
Compound Action Potential ◽  
Average Maximum ◽  
Ionic Changes ◽  
Induced Changes ◽  
Compound Action

In gray matter (GM), anoxia induces prominent extracellular ionic changes that are important in understanding the pathophysiology of this insult. White matter (WM) is also injured by anoxia but the accompanying changes in extracellular ions have not been studied. To provide such information, the time course and magnitude of anoxia-induced changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) were measured in the isolated rat optic nerve, a representative central WM tract, using ion-selective microelectrodes. Anoxia produced less extreme changes in [K+]o and pHo in WM than are known to occur in GM; in WM during anoxia, the average maximum [K+]o was 14 ± 2.9 m M (bath [K+]o = 3 m M) and the average maximum acid shift was 0.31 ± 0.07 pH unit. The extracellular space volume rapidly decreased by ∼20% during anoxia. Excitability of the rat optic nerve, monitored as the amplitude of the supramaximal compound action potential, was lost in close temporal association with the increase in [K+]o Increasing the bath glucose concentration from 10 to 20 m M resulted in a much larger acid shift during anoxia (0.58 ± 0.08 pH unit) and a smaller average increase in [K+]o (9.2 ± 2.6 m M). The increased extracellular glucose concentration presumably provided more substrate for anaerobic metabolism, resulting in more extracellular lactate accumulation (although not directly measured) and a greater acid shift. Enhanced anaerobic metabolism during anoxia would provide energy for operation of ion pumps, including the sodium pump, that would result in smaller changes in [K+]o. These effects were probably responsible for the observation that the optic nerve showed significantly less damage after 60 min of anoxia in the presence of 20 m M glucose compared to 10 m M glucose. Under normoxic conditions, increasing bath K+ concentration to 30 m M (i.e., well beyond the level shown to occur with anoxia) for 60 min caused abrupt loss of excitability during the period of application but minimal change in the amplitude of the compound action potential following the period of exposure. The anoxia-induced increase in [K+]o, therefore, was not itself directly responsible for irreversible loss of optic nerve function. These observations indicate that major qualitative differences exist between mammalian GM and WM with regard to anoxia-induced extracellular ionic changes.

scholarly journals Axon Function Persists during Anoxia in Mammalian White Matter

2003 ◽  
Vol 23 (11) ◽  
pp. 1340-1347 ◽  
Author(s):  
Selva Baltan Tekkök ◽  
Angus M Brown ◽  
Bruce R Ransom
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Anaerobic Capacity ◽  
Compound Action Potential ◽  
Loss Of Function ◽  
Optic Nerves ◽  
Glucose Reduction ◽  
Matter Energy ◽  
Compound Action

Axon function in the CNS has been reported to fail rapidly during anoxia, implying that there is no anaerobic capacity. This phenomenon was reassessed in rodent white matter using mouse or rat optic nerve. Axon function was semiquantitatively measured as area under the compound action potential. Mouse optic nerves exposed to anoxia (30–180 minutes) or cyanide (30–60 minutes) at 37°C exhibited significant persistent function that was abolished by removing glucose. Reduction in compound action potential area increased with anoxia duration reaching a maximum of about 70% after 90 min. Rat optic nerves exposed to anoxia, in contrast to mouse optic nerves, showed rapid and complete loss of function. When artificial CSF glucose was increased from 10 to 30 mmol/L, rat optic nerves responded to anoxia in a similar manner to mouse optic nerves in 10-mmol/L glucose. The authors conclude that white matter is resistant to anoxia with a subset of axons able to subsist exclusively on anaerobically derived energy. Because the rat optic nerve is about twice the diameter of the mouse optic nerve, glucose diffusion into the rat optic nerve was inadequate during anoxia when artificial CSF glucose was 10 mmol/L but became adequate when artificial CSF glucose was 30 mmol/L. These observations have implications for white matter energy metabolism and susceptibility to injury during focal ischemia.

METABOLIC STUDIES WITH 131I-LABELED THYROXINE. II.

1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Pituitary Gland ◽  
Time Interval ◽  
Time Intervals ◽  
Pituitary Glands ◽  
The Central Nervous System ◽  
Tentative Explanation

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

Early Detection of Central Nervous System Relapse of Pediatric Leukemia with Measurement of Optic Nerve Sheath Diameter on MRI

2019 ◽  
Vol 15 (2) ◽  
pp. 237-241
Author(s):  
Taner Arpaci ◽  
Barbaros S. Karagun
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Early Detection ◽  
Optic Nerve Sheath Diameter ◽  
Central Nervous System Relapse ◽  
Mri Findings ◽  
Pediatric Leukemia ◽  
Optic Nerves ◽  
Cns Relapse

Background: Leukemia is the most common pediatric malignancy. Central Nervous System (CNS) is the most frequently involved extramedullary location at diagnosis and at relapse. </P><P> Objective: To determine if Magnetic Resonance Imaging (MRI) findings of optic nerves should contribute to early detection of CNS relapse in pediatric leukemia. Methods: Twenty patients (10 boys, 10 girls; mean age 8,3 years, range 4-16 years) with proven CNS relapse of leukemia followed up between 2009 and 2017 in our institution were included. Orbital MRI exams performed before and during CNS relapse were reviewed retrospectively. Forty optic nerves with Optic Nerve Sheaths (ONS) and Optic Nerve Heads (ONH) were evaluated on fat-suppressed T2-weighted TSE axial MR images. ONS diameter was measured from the point 10 mm posterior to the globe. ONS distension and ONH configuration were graded as 0, 1 and 2. Results: Before CNS relapse, right mean ONS diameter was 4.52 mm and left was 4.61 mm which were 5.68 mm and 5.66 mm respectively during CNS relapse showing a mean increase of 25% on right and 22% on left. During CNS relapse, ONS showed grade 0 distension in 15%, grade 1 in 60%, grade 2 in 25% and ONH demonstrated grade 0 configuration in 70%, grade 1 in 25% and grade 2 in 5% of the patients. Conclusion: MRI findings of optic nerves may contribute to diagnose CNS relapse by demonstrating elevated intracranial pressure in children with leukemia.

Clinical and Genetic Spectrum of 104 Indian families with Central Nervous System White Matter Abnormalities

2021 ◽  
Author(s):  
Parneet Kaur ◽  
Michelle C. Rosario ◽  
Malavika Hebbar ◽  
Suvasini Sharma ◽  
Neethukrishna Kausthubham ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
White Matter Abnormalities
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