A reliable and cost-effective protocol for creating bilirubin cerebral palsy model in rhesus macaque.

BACKGROUND: Cerebral palsy is a severe motor disability in childhood that poses challenges for children, families, and society. Rhesus macaques are the preferred animals for cerebral palsy model, but surgical excision of motor cortex has low success rate and high cost. In this work, we created cerebral palsy rhesus macaque models by intrathecal injection of bilirubin. METHODS: The puncture point for injection was identified as the intervertebral disc space two, located below the intersection of the iliac crest line and the posterior median line. RESULTS: The models showed abnormal posture and increased muscle tension. Diffuse deposits of bilirubin were found in the basal ganglia from the magnetic resonance imaging. Pathological slides also revealed the presence of brain lesions, such as vacuole formation, contraction of neuronal nuclei, and deep staining of nuclei in the histopathological sections of the hippocampus and basal ganglia. CONCLUSION: The model's symptoms closely resemble those observed in humans with spastic cerebral palsy.

Patterns of cerebral injury in a primate model of preterm birth and neonatal intensive care.

Very preterm birth is associated with significant neurodevelopmental morbidity, with 10% to 15% of these infants later developing cerebral palsy and up to 50% experiencing learning disabilities. The nature of the cerebral lesion predisposing these infants to such impairments is not fully understood but is likely related to both cerebral injury and alterations in cerebral development associated with neonatal intensive care. To study the impact of both preterm birth and neonatal intensive care on the immature brain, we are studying a preterm primate model delivered at 125 days of a 184-day gestational period and cared for in a neonatal intensive care unit for 2 to 4 weeks in a fashion highly similar to that for human preterm infants. The most common neuropathology in this model is white-matter damage manifested by reactive astrogliosis or activated microglia and enlarged ventricular size. Subarachnoid, germinal matrix, and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to both the alterations in cerebral developmental and the pattern of cerebral injury found in human preterm infants. We are now investigating the impact of randomized respiratory therapies on the pattern of cerebral injury. The prematurely born baboon appears to be an accurate and relevant model for the study of preterm human birth.

Model of cerebral palsy in the perinatal rabbit.

Perinatal brain injury results in one of the highest burdens of disease in view of the lifelong consequences and is of enormous cost to society. This makes it imperative to develop better animal models that mimic the human condition. Many neurodevelopmental deficits, such as cerebral palsy, are believed to be a result of prenatal hypoxia-ischemia in humans. Fetal global hypoxia-ischemia is most commonly a consequence of acute placental insufficiency. Our laboratory has modeled in utero sustained and repetitive hypoxia-ischemia in the pregnant rabbit to mimic the insults of abruptio placenta and labor, respectively. Sustained hypoxia-ischemia at 70% (22 days' gestation) and 79% (25 days' gestation) and repetitive hypoxia-ischemia at 90% gestation (28 days' gestation) caused stillbirths and multiple deficits in the postnatal survivors. The deficits included impairment in multiple tests of spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and the coordination of suck and swallow. Hypertonia was observed in the 22 and 25 days' gestation survivors but not in the 28 days' gestation group. Hypertonic survivors were artificially fed and found to have the motor deficits persist for at least 11 postnatal days. A spectrum of brain abnormalities is found on magnetic resonance imaging. This is the first animal model to mimic cerebral palsy. The findings also suggest a window of vulnerability during brain development when the injury results in hypertonia in newborn pups.

Hallazgos histopatológicos en bovinos naturalmente afectados por el síndrome neuroparalítico en la Orinoquía colombiana / Histopathological changes in naturally affected bovine by Neuroparalytic Sindrome in Colombian Orinoquía

Como parte de un estudio epidemiológico longitudinal desarrollado en la Altillanura del departamento del Meta durante un año (1998-1999), y con el fin de determinar alteraciones de patología macroscópica y cambios histopatológicos asociados al Síndrome Neuroparalítico Bovino (SNB), se estudiaron 39 bovinos entre 2 y 8 años de edad, los cuales se encontraban afectados naturalmente por esta causa. Se procesaron muestras de 305 tejidos por la técnica de inclusión en parafina, para determinar las principales lesiones histopatológicas. En la necropsia los hallazgos más importantes fueron la presencia de cuerpos extraños (huesos, arcilla, piedras, madera) en el rumen y retículo; en la mayoría de los casos ocurrió compactación del librillo y vesícula biliar pletórica. La congestión de envolturas cerebrales fue una alteración común en todos los casos. Los hallazgos histopatológicos más relevantes incluyeron cambios vasculares en tejido nervioso, dados por edema, congestión, hemorragia e hiperplasia de células endoteliales; cambios grasos intracitoplasmáticos y megalocitosis en hepatocitos; en el riñón, infiltrados mononucleares en glomérulos y túbulos contorneados con vacuolización intracitoplasmática; hialinización y fragmentación de miofibrillas en músculo estriado esquelético y presencia de Sarcocystis bovis y necrosis de Zenker en músculo estriado cardiaco. Se confirma que el Botulismo bovino no produce alteraciones microscópicas de valor; las otras alteraciones son compatibles con NeurotoxicidadRetardada por Pesticidas, deficiencias energéticas y leptospirosis.

[Animal modeling and experimental pharmacology of human spasticity]. / Modélisation animale et pharmacologie expérimentale de la spasticité humaine.

The first part of the paper exposes the basic characteristics of the human spasticity which should be modeled: No hypertonia at rest; velocity-dependent myotatic responses, and fatigability. To model a syndrome including these signs is a related but different problem. Results and limits of the clinical neurophysiology concerning the spasticity are briefly quoted. Animal models would better assist the human neurophysiology when having their neuroanatomy closer to the human one. The second part confirms that a local unilateral excision of the ad hoc sensorimotor cerebral cortice of the Baboon induces a permanent palsy of the contralateral foot and leg, and after delay signs of spasticity in the Sol. Neither clasp-knife phenomenon nor fatigability is observed. There is no sign of motoneuron hyper-excitability. A GABA-related pharmacology suggests a significant defect in the presynaptic inhibition of the reflexogenic IA in-put, and possibly a defect in a post-synaptique gabaergic inhibition. Finally the monkey is considered as a valuable support for modeling the human spasticity, symptom and possibly syndrome.