Postnatal Day 7 Rats Research Articles

Long-Term Beneficial Effects of Erythropoietin Given after Neonatal Stroke in Postnatal Day-7 Rats

Long-Term Beneficial Effects of Erythropoietin Given after Neonatal Stroke in Postnatal Day-7 Rats

Acute and chronic ethanol exacerbates formalin pain in neonatal rats

We have previously reported that withdrawal from acute ethanol (EtOH) exposure lowers mechanical thresholds in post-natal day 7 (P7) and post-natal day 21 (P21) rats. The present study tested the hypothesis that daily administration of 4 g/kg 15% EtOH for 5 days in rats during the human developmental equivalent of the third trimester, but not at a later time in development, would alter mechanical thresholds and formalin-induced pain behaviors. A transient decrease in mechanical thresholds (allodynia) was observed in P7 rats upon withdrawal from repeated EtOH between P3 and P7. When challenged with intraplantar formalin on P11, rats exposed to acute or chronic EtOH had enhanced phase II pain behaviors. In contrast to chronic EtOH administration to rats between P3 and P7, prolonged mechanical allodynia was observed in P21 rats upon withdrawal from chronic EtOH between P17 and P21. Formalin responses were unchanged in P25 rats exposed to acute or chronic EtOH. The affects of EtOH on somatosensory processing are dependent upon the age at which exposure occurs.

Protein kinase c ϵ and γ: roles in age-specific modulation of acute opioid-withdrawal allodynia

Acute morphine withdrawal results in enhanced responsiveness to noxious stimulation in adult humans and rodents. This study extends these findings by demonstrating that acute morphine withdrawal produces allodynia in neonatal rats that is dependent on the translocation of protein kinase C ϵ and γ (ϵPKC and γPKC, respectively) in a developmentally specific manner. Basal expression of ϵPKC in dorsal root ganglia, and γPKC in lamina II of the lumbar spinal cord, were lower in postnatal day 7 (P7) compared with P21 rats. ϵPKC immunoreactivity increased in P7 rats at 4 hours after acute administration of morphine, whereas ϵPKC immunoreactivity decreased at 4 hours in P21 rats. In contrast to ϵPKC, there was a loss of γPKC immunoreactivity following morphine administration in both P7 and P21 rats. To determine whether ϵ and γPKC contribute to acute withdrawal-induced allodynia in neonatal rats, isozyme-specific inhibitors of ϵ and γPKC translocation were administered before or after morphine administration. Naloxone was used to precipitate withdrawal at either 30 or 120 minutes after morphine, or animals were allowed to undergo natural withdrawal from a single dose of morphine. Inhibition of ϵ but not γPKC prevented naloxone-precipitated allodynia 30 minutes after morphine administration in P7 rats. In contrast, both ϵ and γPKC inhibitors attenuated naloxone-precipitated allodynia in P21 rats. Allodynia was attenuated in P7 and P21 rats by administration of either ϵ or γPKC inhibitor when withdrawal was precipitated at 2 hours after morphine or animals underwent natural withdrawal. This work demonstrates that the role of ϵ and γPKC in acute withdrawal-induced allodynia is developmentally regulated in a temporally specific manner.

Heat shock protein 70 expression in neonatal rats after hypoxic stress

Objectives: The tissue damage due to hypoxia in newborns is to some extent age-dependent; organs of premature babies are more vulnerable to hypoxic insult than full-term neonates. The of thisimmunohistochemical study was to investigate the role of heat shock protein 70 (HSP70), a stress-inducible protein, in developing the response to hypoxia in premature newborns.Methods: Postnatalday-7 rats (corresponding to a human fetus of 32-34 weeks' gestation) and day-12 rats (corresponding to a full-term newborn infant) (n = 7) were subjected to mild hypoxia at 33°C. Control rats(n = 7) for each group breathed room air for 4 h. After 4 h of recovery, the animals were killed, and brains, hearts and kidneys were removed for immunohistochemical staining.Results:Immunohistochemically, HSP70 expression was found to be induced in the hippocampus and myocardium after exposure to hypoxia. The level of HSP70 expression in the hippocampus after hypoxic stress was significantlyhigher in the 12-day rats than in the 7-day rats (p = 0.03). However, HSP70 expression in the myocardium did not show any significant difference between the two groups. In addition, no significantinduction of HSP70 expression was apparent in the kidney of rats exposed to hypoxia or in any organ of the control animals.Conclusions: We conclude that diminished HSP70 expression in the hippocampusof premature newborns may play a critical role in developing the response to hypoxic stress. However, HSP70 expression in the heart and the kidney after exposure to hypoxia did not appear to be relatedto fetal maturity.

Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats.

Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.

The non-competitive AMPA antagonist LY 300168 (GYKI 53655) attenuates AMPA-induced hippocampal injury in neonatal rodents

In contrast with the neuroprotective efficacy of competitive and non-competitive N-methyl- d-aspartate (NMDA) antagonists versus NMDA neurotoxicity, reported neuroprotective effects of non-NMDA antagonists in limiting α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) toxicity have been less robust. We tested the effect of the non-competitive AMPA receptor antagonist LY 300168 (GYKI 53655; E. Lilly) (0.25 or 2.5 mg/kg per dose i.p. ×3 doses vs. vehicle) on AMPA-induced excitotoxic injury in postnatal day 7 (P7) rats. To assess specificity, we tested the effect of LY 300168 (2.5 mg/kg per dose ×3 doses) on NMDA-induced excitotoxic injury. P7 rats received right intrahippocampal injections of either ( S)-AMPA (2.5 nmol, n=67) or NMDA (12.5 nmol, n=11). Injection of AMPA resulted in right hippocampal atrophy with pyramidal cell loss. LY 300168 treatment produced dose-dependent attenuation of AMPA-induced right hippocampal injury; based on comparisons with left hippocampal volumes, 2.5 nmol AMPA resulted in 42±3% (mean±SEM) right hippocampal volume loss in controls, but only 10±5% after LY 300168 2.5 mg/kg per dose ( P<0.001; ANOVA). LY 300168 had no effect on NMDA-induced hippocampal injury. The data support the hypothesis that drugs that allosterically regulate AMPA receptor activity can modulate the response of immature brain to AMPA-mediated injury.