scholarly journals Lithium-Mediated Long-Term Neuroprotection in Neonatal Rat Hypoxia–Ischemia is Associated with Antiinflammatory Effects and Enhanced Proliferation and Survival of Neural Stem/Progenitor Cells

2011 ◽  
Vol 31 (10) ◽  
pp. 2106-2115 ◽  
Author(s):  
Hongfu Li ◽  
Qian Li ◽  
Xiaonan Du ◽  
Yanyan Sun ◽  
Xiaoyang Wang ◽  
...  

The aim of this study was to evaluate the long-term effects of lithium treatment on neonatal hypoxic-ischemic brain injury, inflammation, and neural stem/progenitor cell (NSPC) proliferation and survival. Nine-day-old male rats were subjected to unilateral hypoxia–ischemia (HI) and 2 mmol/kg lithium chloride was injected intraperitoneally immediately after the insult. Additional lithium injections, 1 mmol/kg, were administered at 24-hour intervals for 7 days. Animals were killed 6, 24, 72 hours, or 7 weeks after HI. Lithium reduced total tissue loss by 69%, from 89.4±14.6 mm3 in controls ( n = 15) to 27.6 ±6.2 mm3 in lithium-treated animals ( n = 14) 7 weeks after HI ( P<0.001). Microglia activation was inhibited by lithium treatment, as judged by Iba-1 and galectin-3 immunostaining, and reduced interleukin-1β and CCL2 levels. Lithium increased progenitor, rather than stem cell, proliferation in both nonischemic and ischemic brains, as judged by 5-bromo-2-deoxyuridine labeling 24 and 72 hours as well as by phospho-histone H3 and brain lipid-binding protein labeling 7 weeks after HI. Lithium treatment also promoted survival of newborn NSPCs, without altering the relative levels of neuronal and astroglial differentiation. In summary, lithium conferred impressive, morphological long-term protection against neonatal HI, at least partly by inhibiting inflammation and promoting NSPC proliferation and survival.

2005 ◽  
Vol 288 (3) ◽  
pp. R575-R579 ◽  
Author(s):  
Marina Korotkova ◽  
Britt G. Gabrielsson ◽  
Agneta Holmäng ◽  
Britt-Marie Larsson ◽  
Lars Å. Hanson ◽  
...  

Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.


1990 ◽  
Vol 27 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Frederic J Seidler ◽  
Joanne M Bell ◽  
Theodore A Slotkin

1991 ◽  
Vol 130 (2) ◽  
pp. 231-NP ◽  
Author(s):  
H. D. Nicholson ◽  
S. E. F. Guldenaar ◽  
G. J. Boer ◽  
B. T. Pickering

ABSTRACT The long-term effects of oxytocin administration on the testis were studied using intratesticular implants. Adult male rats had an Accurel device containing 20 μg oxytocin (releasing approximately 200 ng/day) implanted into the parenchyma of each testis; control animals received empty devices. The animals were killed at weekly intervals for 4 weeks. Some animals were perfused and the testes processed for light and electron microscopy. Blood was collected from the remaining animals for the measurement of testosterone, dihydrotestosterone, LH, FSH and oxytocin; epididymal sperm counts were measured and the testes were extracted and radioimmunoassayed for testosterone, dihydrotestosterone and oxytocin. Long-term administration of oxytocin resulted in a significant reduction in testicular and plasma testosterone levels throughout the 4-week period examined and, after 14 days of treatment, lipid droplets were seen in the Leydig cells of treated but not control animals. Concentrations of dihydrotestosterone in the plasma and testes of the oxytocin-treated animals, however, were significantly elevated after 7 and 14 days and at no time fell below control values. Plasma FSH levels were also lower in the oxytocin-treated animals. Intratesticular oxytocin treatment did not affect LH or oxytocin concentrations in the plasma, epididymal sperm counts or the number of Leydig cells in the testis. Empty Accurel devices had no effect on testicular morphology. This study provides the first evidence that oxytocin in vivo can modify steroidogenesis in the testis. Journal of Endocrinology (1991) 130, 231–238


2003 ◽  
Vol 8 (4) ◽  
pp. 213-217 ◽  
Author(s):  
C Celeste Johnston ◽  
Claire-Dominique Walker

Preterm infants undergoing untreated, repeated painful procedures as part of their early experience are more likely to behave differently to pain as they mature than infants who were born at term and did not experience excessive exogenous pain. The neonatal rat model was used to investigate the short- and long-term effects of repeated pain in infancy on later development of pain responses. Newborn rat pups were randomly assigned by litter to be left unhandled (UH), handled by being removed from the dam for 15 min four times daily (H), and being handled and receiving pain from a paw prick with a 26G needle four times daily (P)on postnatal days (PD) 2 through 8 (PD2-PD8). Maternal behaviour and grooming of pups on their return to the nest were recorded at PD6 for H and P pups. At PD15, PD36 and PD65, animals were first tested for latency to thermal stimulation threshold using the Hargreaves test and then for inflammatory pain using the formalin test. Pups in the HP group received significantly more grooming from their mothers (359 s) than pups in the H group (295 s, P<0.0001). When accounting for differences in maternal grooming, a decreased thermal threshold in the P group compared with the H group (6.04 s versus 5.3 s, P<0.05) was found, although the correlations were not significant between maternal grooming and thermal thresholds. No group differences were seen with the formalin test. Interestingly, age was a significant factor in both tests, with younger animals showing fewer pain behaviours regardless of group or maternal grooming of the pup. Sex was significant at one age only in latency to thermal stimulation testing. The results suggest that changes in maternal care may be an important factor mediating the long-term effects of repeated neonatal experiences of pain.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1596 ◽  
Author(s):  
Rosa E. Rodríguez-Martínez ◽  
Adán Guillermo Jordán-Garza ◽  
Eric Jordán-Dahlgren

The extraction of tissue-skeleton cores from coral colonies is a common procedure to study diverse aspects of their biology, water quality or to obtain environmental proxies. Coral species preferred for such studies in Caribbean reefs belong to the generaOrbicella. The long term effects of coring in the coral colony are seldom evaluated and in many Caribbean countries this practice is not regulated. We monitored 50 lesions produced onOrbicella faveolatacolonies by the extraction of two centimeter-diameter cores to determine if they were able to heal after a four year period. At the end of the study 4% of the lesions underwent full regeneration, 52% underwent partial regeneration, 14% suffered additional tissue loss but remained surrounded by live tissue, and 30% merged with dead areas of the colonies. Given the low capacity ofOrbicella faveolatato regenerate tissue-skeleton lesions, studies that use coring should be regulated and mitigation actions, such as using less destructive techniques and remediation measures after extraction, should be conducted to facilitate tissue regeneration.


2004 ◽  
Vol 287 (4) ◽  
pp. R934-R942 ◽  
Author(s):  
Magali Lacroix ◽  
Claire Gaudichon ◽  
Antoine Martin ◽  
Céline Morens ◽  
Véronique Mathé ◽  
...  

Although there is a considerable interest of high-protein, low-carbohydrate diets to manage weight control, their safety is still the subject of considerable debate. They are suspected to be detrimental to the renal and hepatic functions, calcium balance, and insulin sensitivity. However, the long-term effects of a high-protein diet on a broad range of parameters have not been investigated. We studied the effects of a high-protein diet in rats over a period of 6 mo. Forty-eight Wistar male rats received either a normal-protein (NP: 14% protein) or high-protein (HP: 50% protein) diet. Detailed body composition, plasma hormones and nutrients, liver and kidney histopathology, hepatic markers of oxidative stress and detoxification, and the calcium balance were investigated. No major alterations of the liver and kidneys were found in HP rats, whereas NP rats exhibited massive hepatic steatosis. The calcium balance was unchanged, and detoxification markers (GSH and GST) were enhanced moderately in the HP group. In contrast, HP rats showed a sharp reduction in white adipose tissue and lower basal concentrations of triglycerides, glucose, leptin, and insulin. Our study suggests that the long-term consumption of an HP diet in male rats has no deleterious effects and could prevent metabolic syndrome.


PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27549 ◽  
Author(s):  
Eva Baquedano ◽  
Cristina García-Cáceres ◽  
Yolanda Diz-Chaves ◽  
Natalia Lagunas ◽  
Isabel Calmarza-Font ◽  
...  

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