The expression of death receptor 6 in the cerebral cortex in neonatal rats after hypoxia ischemia / 临床儿科杂志

Objectives To observe the expression of death receptor 6 (DR6) in neonatal rats with hypoxia-ischemia brain damage (HIBD). Methods HIBD was induced in day 7 rats. The expression of DR6 at 24 h, 72 h and 7 d after HIBD and the expression of Caspase-3 at 24 h were evaluated by immunostaining. The injury of neural cells was evaluated by cresyl violet at 7 d after HIBD. The cognitive function was evaluated by T-maze test at 60 d after HIBD. Results DR6 positive cells were the most abundant in the ipsilateral cortex at 24 h after HIBD, and decreased gradually at 72 h and 7 d after HIBD. There was signiifcant difference of the expression of DR6 among different time points in HIBD group (P<0.01). Compared with control group, DR6 positive cells were more abundant in the ipsilateral cortex at 24 h and 72 h after HIBD (P<0.01) and caspase-3 positive cells were more abundant in the ipsilateral cortex at 24 h after HIBD (P<0.05). The number of cortical neurons were decreased at 7 d after HIBD as compared with control group (P<0.05). The T-maze test showed there was decline of the cognition in HIBD group com-pared with control group (P<0.05). Conclusions The DR6 signaling pathway plays an important role in cerebral cortex injury which may lead to the subsequent neurofunctional deifcits in neonatal HIBD rats.

The immature brain substantia nigra reticulata structure system and epileptic brain injury / 国际儿科学杂志

Epilepsy is a brain dysfunction syndrome resulted from many causes,which is closely related to age,especially occuring in the immature brain.Long-term,repeated seizures can lead to immature brain tissue damage,and increase susceptibility of immature brain to epileptic brain damage.Not only does substantia nigra network have the effect of delicate anticonvulsion,but it is also vulnerable to epilepticseizures.Protecting the immature brain substantia nigra pars can prevent or reduce the risk of seizures,epilepsy has an important role in brain injury recovery.Giving children the brain protective drugs aimed directly at substantia nigra pars is a viable and effective method to treat epileptic brain injury.

Study on the protective function and its mechanism of cyclosporin A to immature brain tissue with convulsive brain damage / 临床儿科杂志

Objective To investigate the protective function and its mechanisms of eyclosporin A to immature brain tissue with convulsive brain damage. Methods 21-day-old SD rats were given lithium-pilocarpine to make the epilepsy model. Total 67 male rats had been investigated. Cyclosporin A (CsA) were injected three times at 6, 30, 54 hrs after model had been established. Three dosages had been chosen: 5, 10 and 25 mg/kg each time. The level of apoptotic cells, P-glycoprotein (P-gp), glial fibrillary acidic protein (GFAP) in CA1 area of hippocampus had been determined, and compared with the rats without giving CsA. Results Rats from epilepsy model group had higher level of apoptosis, P-gp, GFAP expression than those from pseudo-model group. CsA injection by dose 5 mg/kg each time for three times reduced the level of P-gp, GFAP. Model group and pseudo-model group were same. Both the interventions of CsA injection by 10 mg/kg and 25 mg/kg can reduce the level of P-gp, GFAP, however neither of their effectiveness was better than CsA 5 mg/kg each time. Conclusions Small dosage of CsA may protect the immature brain tissue from convulsive brain damage by reducing the level of P-gp, GFAP in CA1 area of hippocampus.

Pathogenesis of brain damage in infant rats induced by corticosteroids / 第三军医大学学报

Objective To explore the possible pathogenesis of brain damage in rats induced by prednisone or corticotrophin. Methods The doses of prednisone or corticotrophin were determined by a primary experiment to obtain corresponding plasma cortisol or corticosterone level as same as that in sick children after drug taking. Then 192 healthy infant (at the age of 7 d) and 192 adult (at the age of 2 months) male SD rats were divided into 4 groups as infant prednisone group, adult prednisone group, infant corticotrophin group and adult corticotrophin group (n=96 in each). then every group was further subdivided into 12 subgroups (n=8 in each). The subgroups were divided according to the dose (therapeutic or low doses), the course [short (10 d) or long (3 weeks)], the sacrificed time (24 h or 4 weeks after withdrawal), and their corresponding controls. Serum neuron-specific enolase (NSE) concentration was quantified by ELISA. Expressions of apoptosis-related proteins, Bax and Bcl-2 in the brain were detected by immunohistochemical assays. Neuronal apoptosis was detected by TUNEL. Results Our primary experiment indicated that the therapeutic dose was 4 mg?kg-1?d-1 or 150 U?m-2?d-1 for prednisone or corticotrophin, and the small dose was 2 mg?kg-1?d-1 or 38 U?m-2?d-1 for them. In infant rats treated with prednisone or corticotrophin at therapeutic-dose for short or long term, their serum NSE concentration were increased significantly by 50.6% to 103.2%. And serum NSE was increased by 38.3% to 60.3% in infant after low-dose treatment for long term. Over-expression of Bax protein (P

Changes in the Levels of Eicosanoids and Isoprostane (8-iso-PGF2alpha) in the Newborn Rat Brain after Hypoxic-Ischemic Injury

PURPOSE: The changes in the levels of eicosanoids and isoprostane (8-iso-PGF2alpha) were investigated in brain tissue of 7 day-old rats after hypoxic-ischemic (HI) injury. METHODS: The 7 day-old newborn rats underwent right unilateral common carotid artery ligation followed by exposure to hypoxia with 8% oxygen for 150 minutes. There after, the pups were decapitated during reoxygenation 21% period of 0, 1, 6, 24, and 72 hours and their cerebral hemisheres were dissected through sagittal plane. Ipsilateral and contralateral cerebral hemesheres to common carotid artery ligation were used to determine the water content for estimation of severity of brain edema (n=5) and to measure the levels of eicosanoid and isoprostane (n=7). The levels of 6-keto-PGF1alpha, TXB2, and PGE2 were measured by RP-HPLC (reversed-phase high-performance liquid chromatography) and the levels of isoprostane (8-iso-PGF2alpha) were measured by enzyme immunoassay. The changes of eicosanoid and isoprostane levels during reoxygenation period were observed and comparisons between ipsilateral and contralateral hemispheres were done. RESULTS: The edema of ipsilateral cerebral hemesheres to common carotid artery ligation was more severe than that of contralateral cerebral hemisheres (P<0.05). The levels of 6-keto-PGF1alpha, TXB2, and PGE2 were found to increase during the early period of reoxygenation after HI insult, peak at 1 hour, and then decrease to the control levels at 72 hour (P<0.05). But, the levels of 8-iso-PGF2alpha did not significantly increase during the period of reoxygenation. The levels of 6-keto-PGF1alpha, TXB2, and PGE2 of ipsilateral hemispheres had a tendency to be higher than those of contralateral hemispheres during the initial 6 hour reoxygenation period, but the levels of 8-iso-PGF2alpha of ipsilateral hemispheres were significantly higher than those of contralateral hemispheres during the relatively later reoxygenation period (P<0.05). CONCLUSION: Reoxygenation after hypoxic-ischemic injury increased the levels of 6-keto-PGF1alpha, TXB2, and PGE2 in 7 day-old rat brain during the early period of reoxygenation, but the levels of isoprostane (8-iso-PGF2alpha) were not significantly increased during the reoxygenation period after HI injury.

The Effect of Pentoxifylline on IL-1beta and TNF-alpha mRNA Gene Expression in Hypoxic-Ischemic Brain Injury of Immature Rat / 대한소아신경학회지

PURPOSE: Interleukin-1beta(IL-1beta) and Tumor necrosis factor-alpha(TNF-alpha) are multifunctional cytokines that may play important roles both in the normal development of central nervous system and in the response of brain to diverse forms of injury. IL-1beta and TNF-alpha have potent proinflammatory action and the potential to modulate cell growth. Cerebral hypoxia-ischemia selectively stimulates IL-1beta and TNF-alpha gene expression in brain regions susceptible to irreversible injury in perinatal rats. Pentoxifylline, a cAMP phosphodiesterase inhibitor, attenuates hypoxic-ischemic brain injury in immature rats and inhibits TNF-alpha expression at the transcription level. We hypothesize that pentoxifylline would attenuate the expression of IL-1beta and TNF-alpha mRNA gene expression on hypoxic-ischemic brain injury in immature rats. METHODS: To elicit focal hypoxic-ischemic brain injury, 7-d-old(P7) rats underwent right carotid artery ligation, followed by 3 hr of hypoxia(fractional concentration of inspired O2=0.08). In 3 rats, pentoxifylline(40mg/kg) was injected into the intraperitoneal cavity immediately before and after hypoxia. The other 4 rats were given PBS solutions. IL-1beta and TNF-alpha mRNA content were measured by reverse transcription followed by polymerase chain reaction amplification(RT-PCR) in the samples prepared from the lesioned and contralateral hemispheres killed 4 hr post-hypoxia. cDNA were amplified with primers specific for IL-1beta and TNF-alpha. and also amplified with GAPDH primers which served as an internal control. RESULTS: In control group, hypoxia-ischemia induced IL-1beta and TNF-alpha mRNA expression from the lesioned hemisphere in immature rat brain. In pentoxifylline treated group, IL-1beta and TNF-alpha mRNA expression were attenuated at 4 hr post hypoxia- ischemia. CONCLUSION: Preteatment with pentoxifylline decreased incidence and severity of hypoxic-ischemic injury in immature rat brain. Pentoxifylline attenuated the expression of IL-1beta and TNF-alpha gene on hypoxic-ischemic injury in immature rat brain. IL-1beta and TNF-alpha may play important roles in the response of the developing brain to acute hypoxic-ischemic injury.

The Effects of Unilateral Brain Hypoxia-ischemia on the Contralateral Cerebral Hemisphere in the Neonatal Rat

Injury to specific areas of the immature brain, in both the human and animals, can result in compensatory reorganization in undamaged adjacent or contralateral areas. The functional plasticity of such compensatory hypertrophy is not well known, but in some cases may be responsible for recovery of function. In order to investigate the effect of unilateral ischemic injury on the contralateral cerebral hemisphere in neonatal rats, early and late changes in various areas of both cerebral hemispheres were assessed. Seventy-seven seven-day-old Sprague-Dawley rats underwent unilateral carotid artery ligation and were then exposed to hypoxia(8% oxygen) for 3 hours. The animals were killed one week(Group I, 58 rats) and three months(Group II, 19 rats) later. Twelve rats, comprising Group III, were exposed to hypoxia for 3 hours without carotid artery ligation. The control group, consisting of 19 rats, did not undergo any of the above procedures. In each slice of brain tissue(4mm posterior to the bregma), the area of the whole brain, each hemisphere, and the frontoparietal, temporal and hippocampal regions in each hemisphere were measured, using the image analysis program(Optimas 5.2), and to assess which regions were affected, proportions of each hemisphere occupied by each region were compared. In Group II, the proportional areas of the frontoparietal(p<0.05) and temporal(p<0.01) regions in the contralateral hemisphere increased significantly, compared with the control group, but the hippocampal region showed no significant change. In Group I, there was no contralateral hypertrophy. The ipsilateral hemisphere showed significant atrophy and there was weight reduction in Groups I(p<0.001) and II(p<0.001). This study suggests that unilateral hypoxia-ischemia results in ipsilateral hemispheric atrophy and contralateral hypertrophy, especially in the frontoparietal and temporal areas, may contribute to some functional recovery and compensation in addition to uncrossed corticospinal or other descending motor systems.