Effects of fetal exposure to lipopolysaccharide, perinatal anoxia and sensorimotor restriction on motor skills and musculoskeletal tissue: implications for an animal model of cerebral palsy

Cerebral palsy (CP) is a disorder of locomotion, posture and movement that can be caused by prenatal, perinatal or postnatal insults during brain development. An increased incidence of CP has been correlated to perinatal asphyxia and maternal infections during gestation. The effects of maternal exposure to low doses of bacterial endotoxin (lipopolysaccharide, LPS) on motor behavior and hind leg muscle morphology were examined in young adult rats. Prenatal exposure to LPS was also studied in association with perinatal anoxia (PA) and/or combined with subsequent sensorimotor restriction (SR) and all possible combinations of the three conditions.Rats exposed to LPS, PA and SR alone or combined (LPS + PA, LPS + SR, PA + SR, and LPS + PA + SR) showed deficits in balance and coordination when tested on the Rotarod. The SR groups, with or without other insults, (SR, LPS + SR, PA + SR, and LPS + PA + SR) exhibited the greatest motor deficits, characterized by the reduced ability to perform the horizontal ladder and suspended bar tests on postnatal day 29 (P29) and P45. Histological assessment revealed substantial morphological alterations in the slow ankle extensor soleus muscle of all SR rats. Soleus myofibers presented a reduction in cross-sectional area (CSA), an increase in sarcomere length and a decrease in sarcomere density. The CSA of the fast flexor tibialis anterior muscle was only decreased by the association of all treatments (LPS, PA, SR), but no differences were found in sarcomere length and density when compared to control. A slow-to-fast fiber type transition was only observed in the soleus and tibialis anterior muscles in the SR groups.These results suggest that exposure to LPS during the prenatal period, PA, SR alone or in combination has various degrees of consequences on motor behavior and muscle morphology. These data corroborate the concept that early experience-dependent movements play the most important role in shaping motor behavior and that reduced or anomalous sensorimotor experience can contribute to the development of aberrant motor behavior and muscle morphology.     

Mild musculoskeletal and locomotor alterations in adult rats with white matter injury following prenatal ischemia

Early brain injury including white matter damage (WMD) appears strongly correlated to perinatal hypoxia-ischemia and adverse neurological outcomes in preterm survivors. Indeed, WMD has been widely associated with subtle to major motor disturbances, sensory, behavioral and cognitive impairments in preterm infants who afterward develop cerebral palsy (CP). Prenatal ischemia (PI) has been shown to reproduce the main features of WMD observed in preterm infants. The present study was aimed at determining in adult rats the impact of PI on brain axons, musculoskeletal histology and locomotor activity. PI was induced by unilateral intrauterine artery ligation at E17 in pregnant rats. We found axonal degeneration and reactive astrogliosis in several white matter regions of adult PI rats. We found mild myopathic and secondary joint changes, including increased variability in myofiber size in several hind limb muscles, decreased myofibers numbers but increased Pax 7 cells and myofiber size in the gastrocnemius, and mild knee and ankle chondromalacia. Although treadmill locomotion appeared normal, several kinematic parameters, such as stride length, amplitude, velocity and leg joint angles were altered in adult PI rats compared to shams. Using intra- and inter-group variability of kinematic parameters, PI seemed to impair the maturation of locomotion on the treadmill. In addition, PI rats exhibited spontaneous hyperactivity in open-field test. Musculoskeletal changes appeared concomitant with mild impairments in gait and posture. Our rodent model of WMD based on PI reproduces the mild motor deficits and musculoskeletal changes observed in many preterm infants with a perinatal history of hypoxia-ischemia, and contributes towards a better understanding of the interplay between brain injury, musculoskeletal histopathology and gait disturbances encountered subsequently.     

Impact of neonatal asphyxia and hind limb immobilization on musculoskeletal tissues and S1 map organization: implications for cerebral palsy

Cerebral palsy (CP) is a complex disorder of locomotion, posture and movements resulting from pre-, peri- or postnatal damage to the developing brain. In a previous study (Strata, F., Coq, J.O., Byl, N.N., Merzenich, M.M., 2004. Comparison between sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy. Neuroscience 129, 141-156.), CP-like movement disorders were more reliably reproduced in rats by hind limb sensorimotor restriction (disuse) during development rather than perinatal asphyxia (PA). To gain new insights into the underpinning mechanisms of CP symptoms we investigated the long-term effects of PA and disuse on the hind limb musculoskeletal histology and topographical organization in the primary somatosensory cortex (S1) of adult rats. Developmental disuse (i.e. hind limb immobilization) associated with PA induced muscle fiber atrophy, extracellular matrix changes in the muscle, and mild to moderate ankle and knee joint degeneration at levels greater than disuse alone. Sensorimotor restricted rats with or without PA exhibited a topographical disorganization of the S1 cortical hind limb representation with abnormally large, multiple and overlapping receptive fields. This disorganization was enhanced when disuse and PA were associated. Altered cortical neuronal properties included increased cortical responsiveness and a decrease in neuronal selectivity to afferent inputs. These data support previous observations that asphyxia per se can generate the substrate for peripheral tissue and brain damage, which are worsened by aberrant sensorimotor experience during maturation, and could explain the disabling movement disorders observed in children with CP.     

Maternal separation activates microglial cells and induces an inflammatory response in the hippocampus of male rat pups,independently of hypothalamic and peripheral cytokine levels

Adult animals subjected to chronic stress show an inflammatory response in the hippocampus which has been related to cognitive dysfunction and psychopathology. However the immediate consequences of early life stress on hippocampal glial cells have not been studied. Here we analyzed the effects of maternal separation (MS) on astrocyte and microglial cell morphology in the hippocampal hilus, compared the expression of cytokines in the hippocampus and hypothalamus, and the peripheral response of cytokines, on postnatal day (PD) 15.Male rat pups of MS (3 h/day, PD1–PD14) and Control (CONT) pups showed similar microglial cell densities in the hilus, but MS pups presented more activated microglia. MS decreased astrocyte density and the number of processes in the hilus. Cytokine mRNA expression (qPCR) was analyzed in MS and CONT groups, sacrificed (i) under basal (B) conditions or (ii) after a single stress event (SS) at PN15. In hippocampal extracts, MS increased IL-1β mRNA, under B and SS conditions while IL-6 and TNF-α did not change. In hypothalamic tissue, MS increased TNF-α and IL-6 mRNA, but not IL-1b, after SS. Peripheral concentrations of IL-1β were decreased under B and SS conditions in MS; IL-6 concentration increased after SS in MS pups, and TNF-α concentration was unchanged. In conclusion, MS activates microglial cells and decreases astrocyte density in the hippocampus. A differential cytokine expression is observed in the hippocampus and the hypothalamus after MS, and after SS. Also, MS triggers an independent response of peripheral cytokines. These specific responses together could contribute to decrease hippocampal neurogenesis and alter the neuroendocrine axis.     

Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium

Many prenatal and perinatal factors are hypothesized to play a role in the cause of cerebral palsy (CP). Epidemiological data implicate maternal-fetal infection and associated increase in circulating cytokines. Murine model data suggest that excitotoxic damage can produce pathological change in brain tissue consistent with lesions observed in CP. Specifically, on day 5 after birth, mouse pups injected with ibotenate, a glutamatergic analogue, develop transcortical necrosis and white matter cysts mimicking some human perinatal lesions associated with CP. The present study builds on this murine model to assess the modulating role of several cytokines on the development of excitotoxic lesions. Pups pretreated with interleukin (IL)-1beta, IL-6, IL-9, or tumor necrosis factor-alpha developed significantly larger ibotenate-induced cortical and white matter damage than controls; IL-4 did not produce such an effect. In a similar manner, IL-9-overexpressing transgenic pups developed ibotenate-induced brain lesions, which were significantly larger than those induced in nontransgenic control pups. Pretreatment with proinflammatory cytokines significantly increased neopallial microglial density without affecting astrocytic density; IL-9 or IL-4 did not produce a similar effect. To our knowledge, this is the first in vivo study to demonstrate that systemically administered proinflammatory cytokines and IL-9 exacerbate brain lesions that are similar to those found in human infants with CP.     

Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: attenuation by N-acetyl cysteine

Cerebral white matter injury during prenatal maternal infection characterized as periventricular leukomalacia is the main substrate for cerebral palsy (CP) in premature infants. Previously, we reported that maternal LPS exposure causes oligodendrocyte (OL)-injury/hypomyelination in the developing brain which can be attenuated by an antioxidant agent, N-acetyl cysteine (NAC). Herein, we elucidated the role of peroxisomes in LPS-induced neuroinflammation and cerebral white matter injury. Peroxisomes are important for detoxification of reactive oxidative species (ROS) and metabolism of myelin-lipids in OLs. Maternal LPS exposure induced selective depletion of developing OLs in the fetal brain which was associated with ROS generation, glutathione depletion and peroxisomal dysfunction. Likewise, hypomyelination in the postnatal brain was associated with decrease in peroxisomes and OLs after maternal LPS exposure. Conversely, NAC abolished these LPS-induced effects in the developing brain. CP brains imitated these observed changes in peroxisomal/myelin proteins in the postnatal brain after maternal LPS exposure. In vitro studies revealed that pro-inflammatory cytokines cause OL-injury via peroxisomal dysfunction and ROS generation. NAC or WY14643 (peroxisome proliferators activated receptor (PPAR)-alpha agonist) reverses these effects of pro-inflammatory cytokines in the wild-type OLs, but not in PPAR-alpha(-/-) OLs. Similarly treated B12 oligodenroglial cells co-transfected with PPAR-alpha siRNAs/pTK-PPREx3-Luc, and LPS exposed PPAR-alpha(-/-) pregnant mice treated with NAC or WY14643 further suggested that PPAR-alpha activity mediates NAC-induced protective effects. Collectively, these data provide unprecedented evidence that LPS-induced peroxisomal dysfunction exacerbates cerebral white matter injury and its attenuation by NAC via a PPAR-alpha dependent mechanism expands therapeutic avenues for CP and related demyelinating diseases.     

Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity

Glial activation during aging was analyzed in primary glia cultured from brain regions sampled across the life span. An initial study showed that phenotypes of activated astrocytes and microglia from aging rat cerebral cortex persisted in primary cultures (Neurobiol. Aging 19 (1998), 97). We extend these findings by examining effects of age on the activation of glial cultures from adult rat brain in response to lipopolysaccharide (LPS), an inflammatory stimulus. Mixed glia from F344 male rats, aged 3 and 24 months, cultured from cerebral cortex (Cx), hippocampus (Hc), and striatum (St), were assayed for cytokines implicated in Alzheimer's disease: IL-1alpha, IL-1beta, IL-6, and TNF-alpha. Regional differences across all age groups included consistently lower expression of these cytokines in glia derived from Cx than Hc and St. Aging increased basal IL-6 mRNA and secretion by >or=3-fold in glia from Cx and Hc. Aging also increased LPS-induced IL-1 and IL-6 in Hc more than in Cx, whereas no significant effects of age were seen in St-derived glial cytokines. TNF-alpha secretion did not differ by donor age (basal or LPS-induced). Nitric oxide production by microglia from Cx of aging brains showed a smaller induction in response to LPS, with proportionately less neurotoxicity. Thus, glial activation during aging shows regional selectivity in cytokine expression, with opposite effects of aging on the increased inducibility of IL-1 and IL-6 vs the decreased production of nitric oxide.     

Hippocampal mossy fiber pathway development in normal and postnatally lead-exposed rats

Lead (Pb)-induced alterations in the postnatal development of the hippocampal formation have recently been suggested as underlying many of the behavioral changes observed after early Pb exposure. This study was thus designed to assess hippocampal mossy fiber pathway (MFP) development in both normal and postnatally Pb-exposed animals. From postnatal days 1 (P1) to 25, Long-Evans hooded rat pups were exposed to Pb through the maternal milk of dams fed 4.0% PbCO₃, by weight, in ground laboratory chow. Control pups suckled dams receiving a Na₂CO₃ control diet. On P25 and P60, weight-matched pairs of Pb-treated and control animals were selected for morphometric evaluation of the MFP following Timm's silver sulfide staining. An increase in the overall length, as well as a reduction in width of the MFP in the CA3 region of the hippocampus of control animals were observed between P25 and P60. Examination of the MFP of P25 Pb-exposed animals indicated severe reductions in the development of this pathway for all parameters measured. At P60, significant reductions in MFP development were still observed in Pb-exposed animals; however, a large degree of recovery in the later-forming parts of the MFP was evident.     

高血压脑出血患者血清和颅内血肿液中IL-1β、IL-6、TNF—α的含量研究

目的通过测定高血压脑出血患者静脉血清及颅内血肿液中白细胞介素-1β（IL-1β）、白细胞介素．6（IL-6）、肿瘤坏死因子-α（TNF—α）水平,探讨这些炎症因子与脑出血病灶及外周血之间的关系。方法在高血压脑出血后24h,72h,7d和14d取80例高血压脑出血患者静脉血清及血肿液检测IL-1β、IL-6、TNF-α的含量（实验组）,并与30例正常体检的患者（对照组）对比。结果高血压脑出血患者血肿液IL-1β、IL-6、TNF-α含量显著高于对照组人群静脉血,并且显著高于实验组患者自身静脉血。实验组患者静脉血清中IL-1β、IL-6、TNF-α含量显著高于对照组人群静脉血清,且病情越重几种炎症因子水平越高。脑出血不同时期静脉血清IL-1β、IL-6、TNF—α．含量比较,在72h最高,此后呈下降趋势。结论高血压脑出血患者IL-1β、IL-6、TNF-α参与了脑出血的炎症反应,是脑出血后脑组织损伤的重要机制之一。     

Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring

An increased incidence of schizophrenia has been associated with several perinatal insults, most notably maternal infection during pregnancy and perinatal hypoxia. This study used a rat model to directly test if maternal exposure to bacterial endotoxin (lipopolysaccharide, LPS) during pregnancy alters behaviors relevant to schizophrenia, in offspring at adulthood. The study also tested if postnatal anoxia interacted with gestational LPS exposure to affect behavior. At adulthood, offspring from dams administered LPS on days 18 and 19 of pregnancy showed significantly increased amphetamine-induced locomotion, compared to offspring from saline-treated dams. A period of anoxia on postnatal day 7 had no effect on amphetamine-induced locomotion and there was no interaction between effects of gestational LPS and postnatal anoxia on this behavior. Offspring from LPS-treated dams also showed enhanced acoustic startle responses as adults, compared to offspring from saline-treated dams. In offspring tested for pre-pulse inhibition (PPI) of acoustic startle and for apomorphine modulation of PPI, no effects of either gestational LPS or of postnatal anoxia and no interactions between LPS and anoxia were observed. It is concluded that maternal LPS exposure during pregnancy in the rat may be a useful model to study mechanisms responsible for effects of maternal infection on behaviors relevant to schizophrenia, in offspring.     

Different effects of anoxia and hind-limb immobilization on sensorimotor development and cell numbers in the somatosensory cortex in rats

Cerebral palsy (CP) is a group of movement and posture disorders attributed to insults in the developing brain. In rats, CP-like motor deficits can be induced by early hind-limb sensorimotor restriction (SR; from postnatal days P2 to P28), associated or otherwise with perinatal anoxia (PA; on P0 and P1). In this study, we address the question of whether PA, early SR or a combination of both produces alterations to sensorimotor development. Developmental milestones (surface righting, cliff aversion, stability on an inclined surface, proprioceptive placing, auditory startle, eye opening) were assessed daily from P3 to P14. Motor skills (horizontal ladder and beam walking) were evaluated weekly (from P31 to P52). In addition, on P52, the thickness of the somatosensory (S1) and cerebellar cortices, and corpus callosum were measured, and the neuronal and glial cell numbers in S1 were counted. SR (with or without PA) significantly delayed the stability on an inclined surface and hastened the appearance of the placing reflex and impaired motor skills. No significant differences were found in the thickness measurements between the groups. Quantitative histology of S1 showed that PA, either alone or associated with SR, increased the number of glial cells, while SR alone reduced neuronal cell numbers. Finally, the combination of PA and SR increased the size of neuronal somata. We conclude that SR impairs the achievement of developmental milestones and motor skills. Moreover, both SR and PA induce histological alterations in the S1 cortex, which may contribute to sensorimotor deficits.     

Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain

Maternal hyperhomocysteinemia is associated with a number of complications such as preeclampsia syndrome, thromboembolic events, repeated miscarriages, abruptio placentae, in utero fetal death, intrauterine fetal growth restriction and fetal neural tube defects. However, little is known about the mechanism of homocysteine on the degeneration of fetal brain. Thus, our study is aimed to investigate the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in pup brain. Hyperhomocysteinemia was induced in female rats by way of administrating methionine dissolved in water at a dose of 1 g/kg body weight throughout the pregnancy. After delivery, level of lipid peroxidation (LPO; as malondialdehyde + 4-hydroxyalkenals) was determined in various fractions of pub brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of LPO in subcellular fractions of pup brains delivered from hyperhomocysteinemic mothers. DNA fragmentation, a hallmark of apoptosis was observed in the brain of pups of homocysteine group while significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. In addition, maternal hyperhomocysteinemia increased cerebral p53 mRNA expression above the control value. As a conclusion, we demonstrate and suggest that the pups of hyperhomocysteinemic mothers have an increased oxidative stress in brain tissues. The increased oxidative stress appears to cause apoptosis and cell death. These results may be significant to understand chronic pathology of the complications of hyperhomocysteinemia and congenital malformations of fetuses.     

Edaravone attenuates cadmium-induced toxicity by inhibiting oxidative stress and inflammation in ICR mice

The neurotoxicity caused by cadmium (Cd) is well known in humans and experimental animals. However, there is no effective treatment for its toxicity. In this study, we established Cd toxicity models in cultured cells or mice to investigate the detoxification effect of edaravone (Eda). We found that Eda protected GL261 cells from Cd toxicity and prevented the loss of cell viability. In Cd-exposed mice, liver, kidney and testicular damage, as well as cognitive dysfunction were observed. Oxidative stress and inflammatory responses, such as decreased SOD and CAT, increased LDH and MDA, and abnormal changes in the inflammatory factors TNF-α, IL-1β, IL-6 and IL-10 were detected in serum and brain tissue. Eda protected mice from Cd-induced toxicity and abrogated oxidative stress and inflammatory responses. Also, Eda prevented inflammatory activation of microglia and astrocytes and was accompanied by restoration of the neuronal marker protein MAP2, indicating restoration of neuronal function. In addition, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the response of Eda to the elimination of Cd toxicity. In conclusion, Eda does contribute to the clearance of Cd-induced toxicity.     

Interleukin-1β-induced brain injury in the neonatal rat can be ameliorated by α-phenyl-n-tert-butyl-nitrone

To examine the possible role of inflammatory cytokines in mediating perinatal brain injury, we investigated effects of intracerebral injection of interleukin-1beta (IL-1β) on brain injury in the neonatal rat and the mechanisms involved. Intracerebral administration of IL-1β (1 μg/kg) resulted in acute brain injury, as indicated by enlargement of ventricles bilaterally, apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. IL-1β also induced axonal and neuronal injury in the cerebral cortex as indicated by elevated expression of β-amyloid precursor protein, short beaded axons and dendrites, and loss of tyrosine hydroxylase-positive neurons in the substantia nigra and the ventral tegmental areas. Administration of α-phenyl-n-tert-butyl-nitrone (PBN, 100 mg/kg i.p.) immediately after the IL-1β injection protected the brain from IL-1β-induced injury. Protection of PBN was linked with the attenuated oxidative stress induced by IL-1β, as indicated by decreased elevation of 8-isoprostane content and by the reduced number of 4-hydroxynonenal or malondialdehyde or nitrotyrosine-positive cells following IL-1β exposure. PBN also attenuated IL-1β-stimulated inflammatory responses as indicated by the reduced activation of microglia. The finding that IL-1β induced perinatal brain injury was very similar to that induced by lipopolysaccharide (LPS), as we previously reported and that PBN was capable to attenuate the injury induced by either LPS or IL-1β suggests that IL-1β may play a critical role in mediating brain injury associated with perinatal infection/inflammation.     

亚低温对外伤性蛛网膜下腔出血患者脑脊液中TNF-α、IL-1和IL-6的影响

目的研究亚低温对外伤性蛛网膜下腔出血脑脊液中TNF-α、IL-1和IL-6的影响,以进一步探讨亚低温对颅脑损伤的治疗作用。方法外伤性蛛网膜下腔出血患者32人,男性23人,女性9人,年龄17~56岁,平均年龄33±7岁,Glasgow分级9±4。分为亚低温组19人,对照组13人。标本采集,患者每天腰穿一次,留取中段脑脊液2ml。立即送实验室检测,TNF-α浓度采用放免法测定,γ放免计数仪检测。IL-1,IL-6浓度采用酶联免疫吸附法测定。结果亚低温组脑脊液TNF-α、IL-1和IL-6浓度除第1天和对照组无明显差异外,其余以后各天均明显增高(P<0.05).结论亚低温可以通过降低脑脊液内TNF、IL-1和IL-6的浓度,参与对外伤性蛛网膜下腔出血的有益治疗作用。     

DIFFERENCES BETWEEN LIPOPOLYSACCHARIDE AND DOUBLE-STRANDED RNA IN INNATE IMMUNE RESPONSES OF BV2 MICROGLIAL CELLS

Microglial cells are thought to be major inflammatory cells in the central nervous system; however, sufficient information about the effects of double-stranded RNA (dsRNA) in microglial cells is lacking. The present study compared the innate immune responses of the murine microglial cell line BV2 to dsRNA and lipopolysaccharide (LPS). It showed that the effect of dsRNA was similar to that of LPS treatment. The dsRNA induced several pro-inflammatory factors such as TNF-α, IL-6, IL-1β, and IL-1Ra. Furthermore, the expression level of COX-2 was increased after treatment with dsRNA. However, the induction level of IL-1β by dsRNA was less than those of the other cytokines that were measured. These results suggest that, although both dsRNA and LPS trigger pro-inflammatory responses, the intracellular signaling pathway and inflammation pattern of dsRNA and LPS may be different. Therefore, dsRNA produced during viral infection could precipitate neurological abnormalities through chronic inflammation.     

Effects of maternal exposure to LPS on the inflammatory response in the offspring

To investigate the effects of maternal infection on the offspring's inflammatory response, pups born to LPS- or saline-treated dams were stimulated with LPS or saline, and the expression of cytokines and chemokines was examined. We found that at P21, pups born to LPS-treated dams exhibited diminished serum levels of TNF-alpha, IL-1beta, and IL-6, and inhibited mRNA levels of cytokines, including TNF-alpha, IL-1beta, and IL-6, and chemokines, including MIP-1beta, MIP-2, and KC, in the brain, as compared to pups born to saline-treated dams at 2 h following LPS stimulation. Our results suggest that maternal infection suppresses the offspring's inflammatory response to LPS.     

Hyperthermia-Induced Seizures in Rat Pups with Preexisting Ischemic Brain Injury

To investigate the mechanism(s) relating perinatal brain injury to increased seizure sensitivity in the developmental age period, we studied hyperthermia-induced seizures in rat pups with a preexisting unilateral ischemic cerebral injury. At 2 days of age, the pups underwent a carotid artery ligation followed by 20 min of anoxia. By light microscopy, there were no pathologic changes in the postischemic cerebral cortex at 5, 10, or 20 days of age. Seizures were induced by hyperthermia at 5, 10, 15, or 20 days of age. Seizure temperature thresholds increased with maturation in both postischemic and control animals. Temperature thresholds for behavioral seizures were significantly lower at 10, 15, and 20 days in postischemic pups, compared with control animals. By EEG criteria, seizure thresholds also were lower at 10 and 15 days in the postischemic pups compared with control animals. Preictal EEG slowing appeared at the same temperature in experimental and control animals at all ages. We conclude that the rat pup is an appropriate model for the study of enhanced epileptogenesis in the presence of a perinatal ischemic encephalopathy.     

急性脑出血患者血清炎症因子和氧化应激产物的动态监测及其临床意义

目的对急性脑出血(AICH)患者血清炎症因子和氧化应激产物水平进行动态监测,探讨急性脑出血后炎症反应与氧化应激的关系及其与疾病的病程及预后的关系。方法选择80例确诊为AICH的患者为研究对象,于入院后24h内、25⁴8h、4948h、49⁷2h、7d、14d分别抽取患者肘静脉血,采用双抗体夹心(ELISA)测定血清炎症因子IL-6及TNF-α水平,黄嘌呤氧化酶法和硫代巴比妥酸法分别测定血清氧化应激产物超氧歧化酶(SOD)和丙二醛(MDA)水平,并于同期进行健康体检的60例正常人群血清IL-6、TNF-α、SOD、MDA进行比较。结果 AICH患者血清IL-6、TNF-α水平、MDA水平24h内即明显上升,至4972h、7d、14d分别抽取患者肘静脉血,采用双抗体夹心(ELISA)测定血清炎症因子IL-6及TNF-α水平,黄嘌呤氧化酶法和硫代巴比妥酸法分别测定血清氧化应激产物超氧歧化酶(SOD)和丙二醛(MDA)水平,并于同期进行健康体检的60例正常人群血清IL-6、TNF-α、SOD、MDA进行比较。结果 AICH患者血清IL-6、TNF-α水平、MDA水平24h内即明显上升,至49⁷2h内达最高值,7d时逐渐下降,14d时基本接近正常;而血清氧化应激产物SOD水平在24h内即开始下降,至4972h内达最高值,7d时逐渐下降,14d时基本接近正常;而血清氧化应激产物SOD水平在24h内即开始下降,至49⁷2h达最低值,而7d时逐渐升高,至14d时基本恢复,与对照组比较差异无统计学意义。结论动态监测血清炎症因子和氧化应激产物变化有利于对脑出血后脑水肿及脑损伤程度的判断以及病情与预后的判定。