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Unable to load video. Please check your Internet connection and reload this page. An unexpected error occurred. Encephalopathy of prematurity encompasses the central nervous system abnormalities associated with injury from preterm birth. This report describes a clinically relevant rat model of in utero transient systemic hypoxia-ischemia and intra-amniotic lipopolysaccharide administration LPS that mimics chorioamnionitis, and the related impact of infectious stimuli and placental underperfusion on CNS development.

Encephalopathy of prematurity EoP is a term that encompasses the central nervous system CNS abnormalities associated with preterm birth. To best advance translational objectives and uncover new therapeutic strategies for brain injury associated with preterm birth, preclinical models of EoP must include similar mechanisms of prenatal global injury observed in humans and involve multiple components of the maternal-placental-fetal system.

Ideally, models should produce a similar spectrum of functional Verletzung des Blutflusses während der Schwangerschaft in the mature animal and Verletzung des Blutflusses während der Schwangerschaft multiple aspects of the pathophysiology.

When combined with intra-amniotic LPS injections, placental inflammation is increased and CNS damage is compounded with associated white matter, gait and imaging abnormalities. Moreover, this model allows for the dissection of inflammation induced by divergent injury types. CNS injury often commences in utero, and is exacerbated by antenatal processes including chorioamnionitis and postnatal complications such as hypoxia and sepsis.

PBI from systemic insults alters Verletzung des Blutflusses während der Schwangerschaft and leads to cerebral palsy, epilepsy, cognitive delay and numerous Verletzung des Blutflusses während der Schwangerschaft disorders affecting emotional regulation, memory and executive function 1,2.

Verletzung des Blutflusses während der Schwangerschaft lack of knowledge hinders real-time diagnosis of CNS injury severity and informed dosing of emerging interventions. Intrauterine inflammation is very common in extreme prematurity and involves a complex fetal-maternal-placental inflammatory cascade 3. Intrauterine infection is often subclinical. Infants who are small for gestational age SGA or who experience infection are exceptionally vulnerable to neurological deficits 3,4.

Further, chorioamnionitis is associated with cognitive impairment at two years 8. Evidence of maternal vascular underperfusion in the placenta Krampfadern Knöchelödem in infants born extremely preterm is also associated with cerebral see more in childhood 9. The synergistic impact of chorioamnionitis and placental perfusion defects is well illustrated by the remarkably high risk of abnormal neurologic outcomes in this patient population at two years of age 10, To mimic human systemic placental perfusion defects and chorioamnionitis associated with pathogen-induced inflammation, we developed a model of prenatal transient systemic hypoxia-ischemia TSHI combined with intra-amniotic lipopolysaccharide LPS in rats.

Our goal was to adapt our model of TSHI alone in rats to include intrauterine inflammation, to facilitate preclinical modeling of CNS injury associated with preterm birth. TSHI alone has revealed persistent loss of oligodendroglial lineage cells, cortical neurons, increased cell death, and elevated pro-inflammatory cytokine levels, with progressive ischemic intervals leading to a graded pattern of injury consistent with prenatal brain injury Modifications to the ischemic components of this model have also demonstrated deficits in memory Verletzung des Blutflusses während der Schwangerschaft, short and long-term memory and mild musculoskeletal alterations in rats as they age Please recommend JoVE to your Verletzung des Blutflusses während der Schwangerschaft. Additionally, prepare post-operative medications in sterile vials including 0.

Also prepare the lipopolysaccharide LPS solution sterilely: Placentas examined on E19 and E21 are grossly edematous with micro-hemorrhage, and necrosis throughout the decidua and labyrinth.

Significant inflammatory infiltrate and increased vascularity is also observed. Brains examined on P2 reveal ventriculomegaly, as well as white matter and subplate neuron loss compared to shams. These data are consistent with impaired developmental upregulation of KCC2 during learn more here critical postnatal period of circuit maturation and these findings are consistent with our prior reports of the effects of TSHI alone in the CA3 hippocampus Please click here to view a larger version of this figure.

EoP is associated with specific cell-type vulnerabilities i. However, significant progress can be made when animal models replicate the human condition as closely as possible. Here, we developed a model a prenatal insult that incorporates the heterogeneity of mechanisms of CNS injury observed in the preterm infant, allowing for subsequent evaluation of visit web page gray and white matter damage and recovery. In humans, ascending bacterial infections weaken the amnion and precipitate premature rupture of membranes.

Additionally, placental perfusion defects stress the placental interface and disrupt placental homeostasis. Thus, placental underperfusion compounds CNS injury from an intrauterine infection. Undeniably, it is challenging to model the common clinical scenario of ascending bacterial infections that precede chorioamnionitis in rodents as they have a duplex uterus.

Each uterine horn has its own cervix, and multiple pregnancies are carried at once. Despite these challenges, preclinical models have been adapted to involve multiple components of the maternal-placental-fetal unit and incorporate in utero inflammation to various degrees.

In the simplest terms, birth does not Therapie Manuelle Krampfadern von to similar points of Varizen Salz development across all animals The model described here can be performed in both pregnant mice and rats, although pup survival in mice is significantly decreased in inexperienced or stressed dams.

The spatiotemporal regulation of neural cell developmental stages of proliferation, migration and differentiation differs amongst various mammals These cell-specific developmental programs influence the vulnerability to injury.

In addition to the applications described, the model described here may be an informative tool for investigation of other Verletzung des Blutflusses während der Schwangerschaft systems impacted by prematurity, including necrotizing enterocolitis NECheart, lung, renal and hypothalamic-pituitary axis dysfunction. Owing to the complexities of LPS pharmacology and differences in maternal and fetal pharmacodynamics, intraperitoneal LPS injections in click at this page are less likely to produce the same fetal inflammatory response shown here.

Further, LPS does not cross the placenta reliably 20, Previously, we attempted direct cervical application of LPS and intrauterine injection similar to what has been described in other mouse models However, we found that mortality and inconsistency of CNS injury was significantly increased among pups within the same litter.

Increasing doses of LPS administered to the amniotic compartment results in increased fetal mortality. LPS has the advantage over direct infection with typical intrauterine gram-negative bacteria in that it activates inflammatory signaling through toll-like receptor 4 without causing active bacterial infection and the associated risk of pathogen spread.

However, this model could be modified to include common pathogens and organisms isolated from human placentas, including group B streptococcuswhich causes placental and neuropathological abnormalities, and autistic-like behavior in rats Similarly, Verletzung des Blutflusses während der Schwangerschaft lipoprotein multiple-banded antigen can simulate Ureaplasma species infection.

Since Ureaplasma is the Verletzung des Blutflusses während der Schwangerschaft common cause of human chorioamnionitis 35this could also be an avenue for future investigation. Verletzung des Blutflusses während der Schwangerschaft of this model include amniotic fluid loss from the intra-amniotic injections. Care must be taken not to use needles larger than 31 G. You must be signed in to post a comment.

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Add to Favorites Sign in to use this feature! Mouse Models of Periventricular Leukomalacia. JoVE has produced over 5, videos demonstrating experiments from laboratories at top research institutions and delivered online to millions of scientists, educators, and students worldwide.

Librarians Users Authors About. Learn more about access Verletzung des Blutflusses während der Schwangerschaft create an account. Use the advanced search feature to refine your search. Sign in with Shibboleth. You must be subscribed to JoVE to access this content. Enter your email to receive a free trial:. Enter your email below to get your free 10 minute trial to JoVE! MedicineIssueInflammationintra-amnioticin uteroratchorioamnionitisplacentapretermintrauterine Jantzie, L.

Gently apply ophthalmic ointment to each eye to prevent corneal drying. Maternal physiology should remain stable throughout the procedure. Surgical Prep and Scrub. Using small animal clippers remove all hair in the lower abdominal region.

Shave in a rectangular pattern with care Behandlung von Krampfadern Schmerzen avoid nicking the nipples or generating razor rash that can be irritating for future nursing of live pups.

Confirm depth of anesthesia via absence of toe-pinch reflex. Using sterile surgical towels, drape the animal. Take care to place the drapes at an appropriate angle such that they maximize the amount of irrigation fluid they absorb whilst not obstructing blood flow to the uterine horns.

Using a scalpel make a 3 cm midline incision in the prepared abdominal skin. Bluntly dissect the skin layer from the abdominal Verletzung des Blutflusses während der Schwangerschaft with scissors. Using forceps and surgical scissors, elevate the abdominal fascial layer and make an incision of the avascular linea alba to gain access to the peritoneal cavity.

Place surgical gauze on the exterior of the incision and moisten with sterile saline. Using blunt forceps and external pressure on the abdomen, gently http: Carefully avoid entanglement and contact with intestines. Arrange fetuses using forceps by contacting only the muscular tissue in between individual amniotic sacs. Expose and isolate the 4 uterine arteries using blunt dissection. Care must be taken to dissect the uterine arteries.

Surrounding tissue and vessels themselves are extremely delicate. Damage to maternal vessels Betrieb Hoden Varizen cause bleeding, and in severe cases, and maternal death. Ensure cessation of blood flow, including proximal and distal pulses, and darkening of the uterine vessels including individual placentas.

Take care to Verletzung des Blutflusses während der Schwangerschaft the field moist with irrigation approximately every 10 min. After 60 min, remove the gauze and irrigate the field.

Ensure that the uterine horns and vessels are adequately moistened for successful clip removal. Gently remove each aneurysm clip using forceps. Take care not to cause trauma to the vessel, and maintain tissue integrity during removal. Thoroughly irrigate the uterine horns and field, taking care to remove any stray threads of gauze from the amniotic sacs.

Injection of Lipopolysaccharide in to Amniotic Sacs. Use blunt forceps to stabilize and rotate each amniotic sac in to an optimal position for injection. Use only an ultra-fine 0. Using larger gauge needles will result in chronic amniotic fluid loss, fetal death and reabsorption of the pregnancy. Small amounts of amniotic fluid leakage upon removal of the syringe can be mitigated by direct pressure to the amniotic sac.

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