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Fisiopatologia dello stress neonatale
1.
2. Il centro del controllo dello stress è l’amigdala, cui fa da supporto l’ippocampo.
All’amigdala arrivano segnali nervosi che mostrano un ambiente ostile o
sconosciuto e l’amigdala risponde facendo partire risposte ormonali in particolare
attivando la produzione di cortisolo
3. PVN Nucleo mediale paraventricolare
dell’ipotalamo
Regolazione neuroendocrina dello stress: recenti acquisizioni FLAVIO POZZI, GAETANO FRAJESE
NÓO ς 3:2004; 143-154
Ma il cortisolo e altri elementi
possono tornare ad amigdala e
ippocampo danneggiandoli
5. Nel neonato l’effetto è simile, ma in più abbiamo due fatti
Un’immaturità e fragilità delle cellule nervose dell’intero encefalo
Una difficoltà visuale e culturale a riconoscere che il neonato soffre lo stress
come e più che un adulto
Gli effetti dello stress sul neonato
sono studiati soprattutto su animali.
E si riferiscono a studi che mostrano
gli effetti sul cervello della
sottrazione della mamma; oppure di
ripetuti stimoli dolorosi
6. • In humans, exposure to childhood abuse or
neglect, for example, has been associated
with an increased risk of anxiety and mood
disorders, obesity, cardiovascular disease
and addiction.
7. anxiety- and depression-
like phenotypes, such as
reduced negative-
feedback of the HPA axis
and Neophobia.
une addiction
pour l’alcool
alterations in
arginine
vasopressin
(AVP) expression
dépendance à la
morphine
by impairments in
learning and memory
tasks such as the
Morris water maze
and novel object
recognition.
increased levels of novelty
induced anxiety, indicated by
increased startle responses,
decreased exploration in
novel environment and
increased latencies to enter a
novel environment
2011
2014
8.
9. Dorsal Root Gamglion
Rostroventral medulla
Periaqueductal Grey Matter Paraventral Nucleus of Hypothalamus
When the animal reaches adulthood, a decrease in phasic inhibitory signalling is observed, due to a selective reduction in glycine receptor (GlyR)-mediated
input to GABAergic and glutamatergic lamina II neurons and a decreased density of tonic GlyR-mediated current in the glutamatergic population (Liet al.,
2013)
10. Figure 1. Cortical thickness at age 7 years in relation to neonatal pain-related stress adjusted for clinical
confounders.
Ranger M, Chau CMY, Garg A, Woodward TS, Beg MF, et al. (2013) Neonatal Pain-Related Stress Predicts Cortical Thickness at
Age 7 Years in Children Born Very Preterm. PLoS ONE 8(10): e76702. doi:10.1371/journal.pone.0076702
http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0076702
11. I meccanismi con cui lo stress danneggia il cervello neonatale
sono vari:
Aumento della pressione del sangue e del liquido cerebrale
Aumento di produzione di aminoacidi eccitatori e radicali liberi
Alterazione dell’espressione di alcuni geni-chiave per l’integrità
del cervello, come quello che regola la pressione (gene della
vasopressina), la plasticità cerebrale e i recettori del cortisone
12.
13.
14.
15. Brain-derived neurotrophic factor)
Marija Kundakovic,Frances A Champagne:
Early-Life Experience, Epigenetics, and the Developing Brain.
Neuropsychopharmacology REVIEWS (2015) 40, 141–153
Nel cervello, è attivo nell'ippocampo, corteccia cerebrale, e prosencefalobasale -
aree vitali per l'apprendimento, la memoria, e il pensiero.
16. Marija Kundakovic,Frances A Champagne:
Early-Life Experience, Epigenetics, and the Developing Brain.
Neuropsychopharmacology REVIEWS (2015) 40, 141–153
The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily
3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind
In rodents, maternal licking
and grooming over the first
days of life cause reduced
HPA-axis reactivity and
anxiety-like behaviors
mediated via increased GR
expression accounted for,
at least in part, by
demethylation at exon 1–7
promoter of the rat GR
gene (Nr3c1) in the
hippocampus of the
offspring.
17. C Murgatroyd.
Translational Psychiatry (2015) 5, e560
Child NR3C1 1-F promoter methylation percent by standardized maternal stroking scores.
The child’s raw methylation percent decreases with maternal stroking for children with mothers who
reported low prenatal but high postnatal depression scores (solid line).
No such decrease is seen for the remainder of the children (dashed).
19. Guzzetta A et al:
The Journal of Neuroscience 2009 •
29(18):6042– 6051
20.
21. E infants showed a significantly smaller increase than C infants in umWM volume
E infants showed decreased coherence (green arrows), likely representing the pruning of C-group
hyper-connectivities
22. Attenzione però alle fonti di stress nascosto.
Lo stesso parto può essere onte di stress, e dipende dal tipo di
parto che il bambino subisce.
E non va dimenticato che il primo fattore di rischio di stress per il
bambino è avere infermieri e medici stressati…
Editor's Notes
Short-term survival of newly generated cells is reduced by stress. A , B , Histological evaluation of BrdU-positive cells in animals examined 1 week after the stress episode (Fig. 1 C, experiment 2) revealed a robust population of BrdU-positive cells in the dentate gyrus of control animals ( A ), but an obvious reduction in cell number for intruder rats ( B ). C–F , Higher magnification of the boxed region shows BrdU-positive cells at various focal planes. Some cells present at one focal plane ( C , D , arrows) are not observed at a deeper focal plane when other BrdU-positive cells come into focus ( E , F , arrowheads). The three-dimensional distribution of cells within the section thickness shows the need for stereological quantitation. Scale bars: A , B , 250 μm; C–F , 25 μm.