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Sidhartha Tan - One of the best experts on this subject based on the ideXlab platform.
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Ascending Lipopolysaccharide-Induced Intrauterine Inflammation in Near-Term Rabbits Leading to Newborn Neurobehavioral Deficits.
Developmental neuroscience, 2018Co-Authors: Zhongjie Shi, Frances J. Northington, Kehuan Luo, Jeannette Vasquez-vivar, Yan Yan, Mohammad Mehrmohammadi, Sidhartha TanAbstract:Background Chorioamnionitis from ascending bacterial infection through the endocervix is a potential risk factor for cerebral palsy. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthase (NOS) and amino acid hydroxylases, when augmented in the fetal brain, prevents some of the cerebral palsy-like deficits in a rabbit hypoxia-ischemia model. Objectives To study the effect of lipopolysaccharide (LPS)-induced intrauterine inflammation in preterm gestation on motor deficits in the newborn, and whether biosynthesis of tetrahydrobiopterin or inflammatory mediators is affected in the fetal brain. Methods Pregnant rabbits at 28 days gestation (89% term) were administered either saline or LPS into both endocervical openings. One group underwent spontaneous delivery, and neurobehavioral tests were performed at postnatal day (P) 1 and P11, with some kits being sacrificed at P1 for histological analysis. Another group underwent Cesarean section 24 h after LPS administration. Gene sequences for rabbit biosynthetic enzymes of tetra-hydrobiopterin pathways were determined and analyzed in addition to cytokines, using quantitative real-time polymerase chain reaction. Results Exposure to 200 μg/kg/mL LPS caused a locomotion deficit and mild Hypertonia at P1. By P11, most animals turned into normal-appearing kits. There was no difference in neuronal cell death in the caudate between hypertonic and nonhypertonic kits at P1 (n = 3-5 in each group). Fetal brain GTP cyclohydrolase I was increased, whereas sepiapterin reductase and 6-pyruvoyltetrahydropterin synthase were decreased, 24 h after LPS administration. Neuronal NOS was also increased. Regardless of the position in the uterus or the brain region, expression of TNF-α and TGF-β was decreased, whereas that of IL-1β, IL-6, and IL-8 was increased (n = 3-4 in each group). Conclusions This is the first study using an ascending LPS-induced intrauterine inflammation model in rabbits, showing mostly transient Hypertonia and mainly locomotor deficits in the kits. Not all proinflammatory cytokines are increased in the fetal brain following LPS administration. Changes in key tetrahydro-biopterin biosynthetic enzymes possibly indicate different effects of the inflammatory insult.
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Elevated spinal monoamine neurotransmitters after antenatal hypoxia-ischemia in rabbit cerebral palsy model.
Journal of neurochemistry, 2015Co-Authors: Alexander Drobyshevsky, Matthew Derrick, Silvia Honda Takada, Kehuan Luo, Katharina A. Quinlan, Jeannette Vasquez-vivar, Maria Inês Nogueira, Sidhartha TanAbstract:We hypothesized that a deficiency in the descending serotonergic input to spinal cord may underlie postnatal muscle Hypertonia after global antenatal hypoxic-ischemic injury in a rabbit model of cerebral palsy. Neurotransmitter content was determined by HPLC in the spinal cord of newborns with and without muscle Hypertonia after fetal global hypoxic-ischemic brain injury and naive controls. Contrary to our hypothesis, serotonin levels in both cervical and lumbar expansions and norepinephrine in cervical expansion were increased in hypertonic kits relative to non-hypertonic kits and controls, with unchanged number of serotonergic cells in caudal raphe by stereological count. Serotonergic fiber length per unit of volume was also increased in hypertonic kits’ cervical and lumbar spinal cord, both in dorsal and ventral horns. Gene expression of serotonin transporter was increased and 5-HTR2 receptors were decreased in hypertonic kits relative to controls in cervical and lumbar cord. Intrathecal administration of nonselective serotonin receptor inhibitor methysergide decreased muscle tone in hypertonic kits only. Conversely, intrathecal administration of serotonin solution increased muscle tone only in non-hypertonic kits. We speculate that maturation of serotonergic system in spinal cord may be directly affected by decreased corticospinal connectivity after antenatal hypoxic-ischemic brain injury.
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Unmyelinated axon loss with postnatal Hypertonia after fetal hypoxia
Annals of neurology, 2014Co-Authors: Alexander Drobyshevsky, Matthew Derrick, Kehuan Luo, Stephen A Back, Rugang Jiang, Laixiang Lin, Sidhartha TanAbstract:Objective White matter (WM) injury due to myelination defects is believed to be responsible for the motor deficits seen in cerebral palsy. We tested the hypothesis that the predominant injury is to functional electrical connectivity in unmyelinated WM fibers by conducting a longitudinal study of central WM tracts in newborn rabbit kits with Hypertonia in our model of cerebral palsy. Methods Pregnant rabbits at 70% gestation underwent 40-minute uterine ischemia. Motor deficits in newborn kits, including muscle Hypertonia, were assessed by neurobehavioral testing. Major central WM tracts, including internal capsule, corpus callosum, anterior commissure, and fimbria hippocampi, were investigated for structural and functional injury using diffusion tensor magnetic resonance imaging (MRI), electrophysiological recordings of fiber conductivity in perfused brain slices, electron microscopy, and immunohistochemistry of oligodendrocyte lineage. Results Motor deficits were observed on postnatal day 1 (P1) when WM tracts were unmyelinated. Myelination occurred later and was obvious by P18. Hypertonia was associated with microstructural WM injury and unmyelinated axon loss at P1, diagnosed by diffusion tensor MRI and electron microscopy. Axonal conductivity from electrophysiological recordings in hypertonic P18 kits decreased only in unmyelinated fibers, despite a loss in both myelinated and unmyelinated axons. Interpretation Motor deficits in cerebral palsy were associated with loss of unmyelinated WM tracts. The contribution of injury to myelinated fibers that was observed at P18 is probably a secondary etiological factor in the motor and sensory deficits in the rabbit model of cerebral palsy. Ann Neurol 2014;75:533–541
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White Matter Injury Correlates with Hypertonia in an Animal Model of Cerebral Palsy
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2006Co-Authors: Alexander Drobyshevsky, Matthew Derrick, Alice M. Wyrwicz, Ila Englof, Lauren Marie Ullman, Mario Enrique Zelaya, Frances J. Northington, Sidhartha TanAbstract:Hypertonia and postural deficits are observed in cerebral palsy and similar abnormalities are observed in postnatal rabbits after antenatal hypoxia-ischemia. To explain why some kits become hypertonic, we hypothesized that white matter injury was responsible for the Hypertonia. We compared newborn kits at postnatal day 1 (P1) with and without Hypertonia after in vivo global fetal hypoxia-ischemia in pregnant rabbits at 70% gestation. The aim was to examine white matter injury by diffusion tensor magnetic resonance imaging indices, including fractional anisotropy (FA). At P1, FA and area of white matter were significantly lower in corpus callosum, internal capsule, and corona radiata of the hypertonic kits (n=32) than that of controls (n=19) while nonhypertonic kits (n=20) were not different from controls. The decrease in FA correlated with decrease in area only in Hypertonia. A threshold of FA combined with area identified only hypertonic kits. A reduction in volume and loss of phosphorylated neurofilaments in corpus callosum and internal capsule were observed on immunostaining. Concomitant Hypertonia with ventriculomegaly resulted in a further decrease of FA from P1 to P5 while those without ventriculomegaly had a similar increase of FA as controls. Thus, Hypertonia is associated with white matter injury, and a population of Hypertonia can be identified by magnetic resonance imaging variables. The white matter injury manifests as a decrease in the number and density of fiber tracts causing the decrease in FA and volume. Furthermore, the dynamic response of FA may be a good indicator of the plasticity and repair of the postnatal developing brain.
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preterm fetal hypoxia ischemia causes Hypertonia and motor deficits in the neonatal rabbit a model for human cerebral palsy
The Journal of Neuroscience, 2004Co-Authors: Matthew Derrick, Ning Ling Luo, Joanne C Bregman, Tamas Jilling, Kara Fisher, Candece L Gladson, Douglas J Beardsley, Geoffrey Murdoch, Stephen A Back, Sidhartha TanAbstract:Prenatal hypoxia-ischemia to the developing brain has been strongly implicated in the subsequent development of the hypertonic motor deficits of cerebral palsy (CP) in premature and full-term infants who present with neonatal encephalopathy. Despite the enormous impact of CP, there is no animal model that reproduces the Hypertonia and motor disturbances of this disorder. We report a rabbit model of in utero placental insufficiency, in which Hypertonia is accompanied by marked abnormalities in motor control. Preterm fetuses (67-70% gestation) were subjected to sustained global hypoxia. The dams survived and gave spontaneous birth. At postnatal day 1, the pups that survived were subjected to a battery of neurobehavioral tests developed specifically for these animals, and the tests were videotaped and scored in a masked manner. Newborn pups of hypoxic groups displayed significant impairment in multiple tests of spontaneous locomotion, reflex motor activity, and the coordination of suck and swallow. Increased tone of the limbs at rest and with active flexion and extension were observed in the survivors of the preterm insult. Histopathological studies identified a distinct pattern of acute injury to subcortical motor pathways that involved the basal ganglia and thalamus. Persistent injury to the caudate putamen and thalamus at P1 was significantly correlated with hypertonic motor deficits in the hypoxic group. Antenatal hypoxia-ischemia at preterm gestation results in Hypertonia and abnormalities in motor control. These findings provide a unique behavioral model to define mechanisms and sequelae of perinatal brain injury from antenatal hypoxia-ischemia.
Bruce Elliott - One of the best experts on this subject based on the ideXlab platform.
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Lycra® arm splints improve movement fluency in children with cerebral palsy
Gait & Posture, 2010Co-Authors: Catherine Elliott, Jacqueline Alderson, Peter Hamer, Siobhan Reid, Bruce ElliottAbstract:Aims: To determine changes in upper limb movement substructures that denote fluency of movement in children with cerebral palsy (CP) following lycra 1 splint wear. Secondarily, to explore the efficacy of lycra 1 splints for those with spastic and dystonic Hypertonia. Design: Randomised clinical trial whereby participants were randomised to parallel groups with waiting list control. Method: Sixteen children (mean age 11.5 years SD = 2.2) with hypertonic upper limb involvement (13 hemiplegia, 4 quadriplegia) were recruited. Children were randomly allocated either to a control group or to wear the lycra 1 splint for a period of three months. Three-dimensional (3D) upper limb kinematics was used to assess four functional tasks at baseline, on initial lycra 1 splint application, three months after lycra 1 splint wear, and immediately after splint removal. Movement substructures of the motion of the wrist joint center were analysed. Results: A significant difference was observed between baseline and three months of lycra 1 splint wear in the movement substructures; movement time, percentage of time and distance in primary movement, jerk index, normalised jerk and percentage of jerk in primary and secondary movements. The magnitude of changes in normalised jerk and the percentage of jerk in the primary movement from baseline to three months was greatest in children with dystonic Hypertonia. Conclusions: The results indicate that lycra
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Lycra ® arm splints improve movement fluency in children with cerebral palsy
Gait & Posture, 2010Co-Authors: Catherine Elliott, Jacqueline Alderson, Peter Hamer, Siobhan Reid, Bruce ElliottAbstract:Aims: To determine changes in upper limb movement substructures that denote fluency of movement in children with cerebral palsy (CP) following lycra 1 splint wear. Secondarily, to explore the efficacy of lycra 1 splints for those with spastic and dystonic Hypertonia. Design: Randomised clinical trial whereby participants were randomised to parallel groups with waiting list control. Method: Sixteen children (mean age 11.5 years SD = 2.2) with hypertonic upper limb involvement (13 hemiplegia, 4 quadriplegia) were recruited. Children were randomly allocated either to a control group or to wear the lycra 1 splint for a period of three months. Three-dimensional (3D) upper limb kinematics was used to assess four functional tasks at baseline, on initial lycra 1 splint application, three months after lycra 1 splint wear, and immediately after splint removal. Movement substructures of the motion of the wrist joint center were analysed. Results: A significant difference was observed between baseline and three months of lycra 1 splint wear in the movement substructures; movement time, percentage of time and distance in primary movement, jerk index, normalised jerk and percentage of jerk in primary and secondary movements. The magnitude of changes in normalised jerk and the percentage of jerk in the primary movement from baseline to three months was greatest in children with dystonic Hypertonia. Conclusions: The results indicate that lycra
Sam C Colachis - One of the best experts on this subject based on the ideXlab platform.
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severe trismus as a complication of cerebrovascular accident a case report
Archives of Physical Medicine and Rehabilitation, 2005Co-Authors: Vivek Kadyan, Albert C Clairmont, Michael T Engle, Sam C ColachisAbstract:Abstract Kadyan V, Clairmont AC, Engle M, Colachis SC. Severe trismus as a complication of cerebrovascular accident: a case report. Spastic Hypertonia is a common sequelae after a cerebrovascular accident (CVA) and is a component of an upper motoneuron lesion. Management of spastic Hypertonia may involve the use of centrally acting agents, peripheral blockade, and ablative therapies. We report a case of spastic Hypertonia leading to severe trismus after CVA that was successfully treated with botulinum toxin type A. Severe trismus is a potentially life-threatening condition that may lead to permanent functional impairment if not promptly diagnosed and treated. Using electromyography for botulinum toxin muscle selection in this case appears to have helped decrease the dose of botulinum toxin given as well as minimize potential side effects.
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severe trismus as a complication of cerebrovascular accident a case report
Archives of Physical Medicine and Rehabilitation, 2005Co-Authors: Vivek Kadyan, Albert C Clairmont, Michael T Engle, Sam C ColachisAbstract:Spastic Hypertonia is a common sequelae after a cerebrovascular accident (CVA) and is a component of an upper motoneuron lesion. Management of spastic Hypertonia may involve the use of centrally acting agents, peripheral blockade, and ablative therapies. We report a case of spastic Hypertonia leading to severe trismus after CVA that was successfully treated with botulinum toxin type A. Severe trismus is a potentially life-threatening condition that may lead to permanent functional impairment if not promptly diagnosed and treated. Using electromyography for botulinum toxin muscle selection in this case appears to have helped decrease the dose of botulinum toxin given as well as minimize potential side effects.
Catherine Elliott - One of the best experts on this subject based on the ideXlab platform.
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Lycra® arm splints improve movement fluency in children with cerebral palsy
Gait & Posture, 2010Co-Authors: Catherine Elliott, Jacqueline Alderson, Peter Hamer, Siobhan Reid, Bruce ElliottAbstract:Aims: To determine changes in upper limb movement substructures that denote fluency of movement in children with cerebral palsy (CP) following lycra 1 splint wear. Secondarily, to explore the efficacy of lycra 1 splints for those with spastic and dystonic Hypertonia. Design: Randomised clinical trial whereby participants were randomised to parallel groups with waiting list control. Method: Sixteen children (mean age 11.5 years SD = 2.2) with hypertonic upper limb involvement (13 hemiplegia, 4 quadriplegia) were recruited. Children were randomly allocated either to a control group or to wear the lycra 1 splint for a period of three months. Three-dimensional (3D) upper limb kinematics was used to assess four functional tasks at baseline, on initial lycra 1 splint application, three months after lycra 1 splint wear, and immediately after splint removal. Movement substructures of the motion of the wrist joint center were analysed. Results: A significant difference was observed between baseline and three months of lycra 1 splint wear in the movement substructures; movement time, percentage of time and distance in primary movement, jerk index, normalised jerk and percentage of jerk in primary and secondary movements. The magnitude of changes in normalised jerk and the percentage of jerk in the primary movement from baseline to three months was greatest in children with dystonic Hypertonia. Conclusions: The results indicate that lycra
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Lycra ® arm splints improve movement fluency in children with cerebral palsy
Gait & Posture, 2010Co-Authors: Catherine Elliott, Jacqueline Alderson, Peter Hamer, Siobhan Reid, Bruce ElliottAbstract:Aims: To determine changes in upper limb movement substructures that denote fluency of movement in children with cerebral palsy (CP) following lycra 1 splint wear. Secondarily, to explore the efficacy of lycra 1 splints for those with spastic and dystonic Hypertonia. Design: Randomised clinical trial whereby participants were randomised to parallel groups with waiting list control. Method: Sixteen children (mean age 11.5 years SD = 2.2) with hypertonic upper limb involvement (13 hemiplegia, 4 quadriplegia) were recruited. Children were randomly allocated either to a control group or to wear the lycra 1 splint for a period of three months. Three-dimensional (3D) upper limb kinematics was used to assess four functional tasks at baseline, on initial lycra 1 splint application, three months after lycra 1 splint wear, and immediately after splint removal. Movement substructures of the motion of the wrist joint center were analysed. Results: A significant difference was observed between baseline and three months of lycra 1 splint wear in the movement substructures; movement time, percentage of time and distance in primary movement, jerk index, normalised jerk and percentage of jerk in primary and secondary movements. The magnitude of changes in normalised jerk and the percentage of jerk in the primary movement from baseline to three months was greatest in children with dystonic Hypertonia. Conclusions: The results indicate that lycra
Vivek Kadyan - One of the best experts on this subject based on the ideXlab platform.
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severe trismus as a complication of cerebrovascular accident a case report
Archives of Physical Medicine and Rehabilitation, 2005Co-Authors: Vivek Kadyan, Albert C Clairmont, Michael T Engle, Sam C ColachisAbstract:Abstract Kadyan V, Clairmont AC, Engle M, Colachis SC. Severe trismus as a complication of cerebrovascular accident: a case report. Spastic Hypertonia is a common sequelae after a cerebrovascular accident (CVA) and is a component of an upper motoneuron lesion. Management of spastic Hypertonia may involve the use of centrally acting agents, peripheral blockade, and ablative therapies. We report a case of spastic Hypertonia leading to severe trismus after CVA that was successfully treated with botulinum toxin type A. Severe trismus is a potentially life-threatening condition that may lead to permanent functional impairment if not promptly diagnosed and treated. Using electromyography for botulinum toxin muscle selection in this case appears to have helped decrease the dose of botulinum toxin given as well as minimize potential side effects.
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severe trismus as a complication of cerebrovascular accident a case report
Archives of Physical Medicine and Rehabilitation, 2005Co-Authors: Vivek Kadyan, Albert C Clairmont, Michael T Engle, Sam C ColachisAbstract:Spastic Hypertonia is a common sequelae after a cerebrovascular accident (CVA) and is a component of an upper motoneuron lesion. Management of spastic Hypertonia may involve the use of centrally acting agents, peripheral blockade, and ablative therapies. We report a case of spastic Hypertonia leading to severe trismus after CVA that was successfully treated with botulinum toxin type A. Severe trismus is a potentially life-threatening condition that may lead to permanent functional impairment if not promptly diagnosed and treated. Using electromyography for botulinum toxin muscle selection in this case appears to have helped decrease the dose of botulinum toxin given as well as minimize potential side effects.