NEUROPROTECTIVE EFFECT OF GROWTH HORMONE (GH) IN HYPOXIC ORGANOTYPIC CULTURES OF CHICKEN CEREBELLUM

The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

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Age-dependent neuroprotective effect of an SK3. channel agonist on excitotoxity to dopaminergic neurons in organotypic culture

10.1101/784009 ◽

2019 ◽

Author(s):

Oscar Maldonado ◽

Alexandra Jenkins ◽

Helen M. Belalcazar ◽

Katelynn M. Hyman ◽

Helena-Hernandez Cuervo ◽

...

Keyword(s):

Developmental Stage ◽

Dopaminergic Neurons ◽

Neuroprotective Effect ◽

Organotypic Cultures ◽

Significant Toxicity ◽

Calcium Activated Potassium Channel ◽

Small Conductance ◽

Sk3 Channel ◽

Channel Agonist

AbstractWe evaluated the age-dependency of the neuroprotective effect of an small-conductance calcium activated potassium channel 3 (SK3) agonist, 1-EBIO, on AMPA excitoxicity to dopaminergic neurons (DN) in organotypic cultures. Most TH+ neurons were also SK3+. SK3+/TH-cells (DN+) were common at each developmental stage but more prominently at day in vitro (DIV) 8. Young DN+ neurons were small bipolar and fusiform, whereas mature ones were large and multipolar. Exposure of organotypic cultures to AMPA (100 μm, 16 h) had no effect on the survival of DN+ at DIV 8, but caused significant toxicity at DIV 15 (n=15, p=0.005) and DIV 22 (n=15, p<<0.001). These results indicate that susceptibility of DN to AMPA excitotoxicity is developmental stage-dependent in embryonic VM organotypic cultures. Immature DN+ (small, bipolar) were increased after AMPA (100 μm, 16 h) at DIV 8, at the expense of the number of differentiated (large, multipolar) DN+ (p=0.039). This effect was larger at DIV 15 (p<<<0.0001) and at DIV 22 (p<<<0.0001). At DIV 8, 30 μM 1-EBIO resulted in a large increase in DN+. At DIV 15, AMPA toxicity was prevented by exposure to 30 μM, but not 100 μM 1-EBIO. At DIV 22, excitotoxicity was unaffected by 30 μM 1-EBIO, and partially reduced by 100 μM 1-EBIO. The effects of the SK3. channel agonist 1-EBIO on the survival of SK3.-expressing dopaminergic neurons were concentrationdependent and influenced by neuronal developmental stage.

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Neuroprotective Effect of GPE Pretreatment on Rat Hippocampal Organotypic Cultures Exposed to NMDA

IGFs in the Nervous System ◽

10.1007/978-88-470-2246-1_13 ◽

1998 ◽

pp. 145-150

Author(s):

L. Curatolo ◽

G. L. Raimondi ◽

C. Caccia ◽

E. Wong ◽

S. Gatti ◽

...

Keyword(s):

Neuroprotective Effect ◽

Organotypic Cultures

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Neuroprotective effect of epidermal growth factor plus growth hormone-releasing peptide-6 resembles hypothermia in experimental stroke

Neurological Research ◽

10.1080/01616412.2016.1235249 ◽

2016 ◽

Vol 38 (11) ◽

pp. 950-958 ◽

Cited By ~ 3

Author(s):

N. Subirós ◽

H. Pérez-Saad ◽

L. Aldana ◽

C. L. Gibson ◽

W. S. Borgnakke ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Neuroprotective Effect ◽

Experimental Stroke ◽

Epidermal Growth

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Decision letter for "Neurochemical phenotype of growth hormone‐responsive cells in the mouse paraventricular nucleus of the hypothalamus"

10.1002/cne.25017/v2/decision1 ◽

2020 ◽

Keyword(s):

Growth Hormone ◽

Paraventricular Nucleus

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Association of pituitary adenoma with neuronal christoma: A TEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010016889x ◽

1994 ◽

Vol 52 ◽

pp. 232-233

Author(s):

Eva Horvath ◽

Kalman Kovacs ◽

B. W. Scheithauer ◽

R. V. Lloyd ◽

H. S. Smyth

Keyword(s):

Growth Hormone ◽

Pituitary Adenoma ◽

Pituitary Tumor ◽

Nervous Tissue ◽

Alternative Explanation ◽

Growth Hormone Releasing Hormone ◽

Cell Hyperplasia ◽

Releasing Hormone ◽

Secretory Neurons

The association of a pituitary adenoma with nervous tissue consisting of neuron-like cells and neuropil is a rare abnormality. In the majority of cases, the pituitary tumor is a chromophobic adenoma, accompanied by acromegaly. Histology reveals widely variable proportions of endocrine and nervous tissue in alternating or intermingled patterns. The lesion is perceived as a composite one consisting of two histogenetically distinct parts. It has been suggested that the neuronal component, morphologically similar to secretory neurons of the hypothalamus, may initiate adenoma formation by releasing stimulatory substances. Immunoreactivity for growth hormone releasing hormone (GRH) in the neuronal component of some cases supported this view, whereas other findings such as consistent lack of growth hormone (GH) cell hyperplasia in the lesions called for alternative explanation.Fifteen tumors consisting of a pituitary adenoma and a neuronal component have been collected over a 20 yr. period. Acromegaly was present in 11 patients, was equivocal in one, and absent in 3.

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