scholarly journals Elevated spinal monoamine neurotransmitters after antenatal hypoxia-ischemia in rabbit cerebral palsy model

2015 ◽  
Vol 132 (4) ◽  
pp. 394-402 ◽  
Author(s):  
Alexander Drobyshevsky ◽  
Silvia Honda Takada ◽  
Kehuan Luo ◽  
Matthew Derrick ◽  
Lei Yu ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Monoamine Neurotransmitters ◽  
Antenatal Hypoxia ◽  
Hypoxia Ischemia

Sensory deficits and olfactory system injury detected by novel application of MEMRI in newborn rabbit after antenatal hypoxia–ischemia

NeuroImage ◽  
2006 ◽  
Vol 32 (3) ◽  
pp. 1106-1112 ◽  
Author(s):  
Alexander Drobyshevsky ◽  
Alan M. Robinson ◽  
Matthew Derrick ◽  
Alice M. Wyrwicz ◽  
Xinhai Ji ◽  
...  
Keyword(s):  
Olfactory System ◽  
Antenatal Hypoxia ◽  
Sensory Deficits ◽  
Newborn Rabbit ◽  
Hypoxia Ischemia

Human Umbilical Cord Mesenchymal Stem Cells Efficiently Improve Neurobehavioral Status and Alleviate Brain Injury in Hypoxia/Ischemia-Induced Cerebral Palsy Rat Model Via Down-Regulating the Nogoa/Ngr/Rho Pathway

2021 ◽  
Author(s):  
Yaoling Luo ◽  
Zhengyi He ◽  
Minhong Zhang ◽  
Zhengwei Zou ◽  
Lincai Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Mesenchymal Stem Cells ◽  
Cerebral Palsy ◽  
Brain Injury ◽  
Umbilical Cord ◽  
Rat Model ◽  
Human Umbilical Cord ◽  
Hypoxia Ischemia ◽  
Brain Tissues

Abstract Background: Cerebral palsy (CP) is a brain injury disease, which is a global public health issue with an estimated prevalence of 2‰—4‰ and imposes a substantial health burden on many countries. At present, there is no ideal treatment available and most of them will still suffer adverse outcomes. Human umbilical cord mesenchymal stem cells(HUCMSCs) application in many fields of medicine, which can promote nervous system regeneration and inhibit neuroinflammation. The regeneration of central nervous system(CNS) is related to the nervous regeneration inhibitors. NogoA/NgR/Rho pathway is very important to the nerve growth, CP injury is inevitably accompanied by the regeneration and repair of neurons and axons. so we hypothesized that NogoA/NgR/Rho pathway is involved in when using the HUCMSCs to treatment cerebral palsy.Purpose: In this study, we might clarify the NogoA/NgR/Rho pathway functional role in mediating HUCMSCs to improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP rat model.Methods: The CP rat model was established by ligating the left common carotid artery and anoxia for 2.5 h, and HUCMSCs were intravenous injected to the modeled rats. The neurobehavioral situation and brain pathological injury in CP rats were determined via a series of assays. The mRNA and protein expression of NogoA、NgR、RhoA、Rac-1、Cdc42 in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. Results: The CP rats exhibited obvious motor function abnormalities, pathological damage and a lot of brain nerve cell apoptosis. Compared with CP+PBS group and CP group rats, HUCMSCs transplantation can significantly improve the neurobehavioral situation, attenuated brain pathological injury, inhibit apoptosis of brain nerve cells and the activation of astrocytes in CP rats. The expression of NogoA、NgR、RhoA relative mRNA and protein in brain tissues of rats in the CP+PBS group and CP group rats were significantly lower than those of in the sham+PBS and CP+HUCMSCs group. The expression of Rac-1、Cdc42 relative mRNA and protein in brain tissues of rats in the sham and CP+HUCMSCs group was significantly higher than those of in CP+PBS group and CP group rats. Conclusion: This study confirmed that HUCMSCs can efficiently improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced cerebral palsy rat model via down-regulating the NogoA/NgR/Rho pathway.

scholarly journals Rodent Hypoxia–Ischemia Models for Cerebral Palsy Research: A Systematic Review

2016 ◽  
Vol 7 ◽  
Author(s):  
Prakasham Rumajogee ◽  
Tatiana Bregman ◽  
Steven P. Miller ◽  
Jerome Y. Yager ◽  
Michael G. Fehlings
Keyword(s):  
Systematic Review ◽  
Cerebral Palsy ◽  
Hypoxia Ischemia

scholarly journals Altered Motoneuron Properties Contribute to Motor Deficits in a Rabbit Hypoxia-Ischemia Model of Cerebral Palsy

2020 ◽  
Vol 14 ◽  
Author(s):  
Preston R. Steele ◽  
Clarissa Fantin Cavarsan ◽  
Lisa Dowaliby ◽  
Megan Westefeld ◽  
N. Katenka ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Motor Deficits ◽  
Hypoxia Ischemia

scholarly journals Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairments and cerebral palsy

Redox Biology ◽  
2017 ◽  
Vol 13 ◽  
pp. 594-599 ◽  
Author(s):  
Jeannette Vasquez-Vivar ◽  
Zhongjie Shi ◽  
Kehuan Luo ◽  
Karthikeyan Thirugnanam ◽  
Sidhartha Tan
Keyword(s):  
Cerebral Palsy ◽  
Motor Impairments ◽  
Brain Hypoxia ◽  
Hypoxia Ischemia

Abstract 3575: Oligodendrocyte Proliferation and Improved Myelination Following Human Embryonic-Derived Neural Stem Cell Treatment in an Experimental Model of Cerebral Palsy

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tenille Smith ◽  
Sahar Rosenblum ◽  
Nancy Wang ◽  
Sam Lawrence ◽  
Kendrick Wang ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Stem Cell ◽  
White Matter ◽  
Corpus Callosum ◽  
Neural Stem Cell ◽  
Functional Recovery ◽  
White Matter Injury ◽  
Motor Disability ◽  
Hypoxia Ischemia

Introduction: Cerebral palsy (CP) is the most common cause of motor disability in children, and chronic deficits are associated with white matter injury. Neonatal hypoxic-ischemic insults, an important cause of CP, induce oligodendrocyte apoptosis and impair normal myelin development. No CP treatments target myelination making regenerative medicine a promising research frontier. We investigated the effect of human embryonic-derived neural stem cell (NSC) treatment on oligodendrocytes and myelination following hypoxia-ischemia (HI). Methods: Neonatal Wistar rat pups underwent left CCA ligation followed by placement in 8% O2 at 37°C on post-natal day 7 (P7). Following T2w MRI on P9, immunosuppressed pups received intra-arterial transplant of 500k fLuc/eGFP transduced NSCs or saline on P10. BrdU was administered intraperitoneally from P11 - P18. In vivo bioluminescence images (BLI) were obtained 1 - 10 days (d) after injection. Myelination was evaluated using luxol fast blue (LFB) and myelin basic protein (MBP) staining 10 and 30 d after treatment. Oligodendrogenesis was quantified using BrdU staining in conjunction with Olig2, NG2, and CC1. RT-qPCR was performed on neonatal brain isolates and NSC mRNA. Luminex immunological assay was used to quantify NSC protein secretion. Functional recovery was assessed using the novel object recognition (NOR) task at P30. Results: Stroke size between groups was not significantly different 3, 10, and 30 d after treatment. BLI demonstrated significant NSC homing to the ischemic hemisphere days 1 - 7 (p=0.001) after transplant. Histology confirmed initial NSC localization to corpus callosum and cortex with migration into external capsule and corona radiata 30 d after transplant. NSC-treated pups had significantly more BrdU+ cells near the lateral ventricle (p=0.036) and in the corpus callosum (p=0.020) than controls. In addition to more Olig2+ and NG2+ cells in the striatum, NSC-treated pups had significantly more BrdU+/Olig2+ cells in the corpus callosum (p<0.05) than controls 30 d after treatment. LFB and MBP staining demonstrated greater myelination 10 and 30 d after treatment in corpus callosum (p=0.022, p<0.05) and striatum (p=0.017, p=0.001) of NSC-treated pups. Stat3 (2.82), IL-6 (1.48), and IL-6Rβ (1.73) mRNA was upregulated in the brains of NSC-treated pups. Proteomic and mRNA data confirm NSC expression of VEGF (17.9pg/mL, 4.35) and CXCL1 (3.6pg/mL, 10.27). NSC-treated pups performed better on NOR (p=0.016). Conclusions: Intra-arterial NSC transplant after hypoxia-ischemia results in NSC engraftment into white matter tracts, increased oligodendrocyte proliferation, and improved myelination. NSC-derived proteins may drive the distinct changes in gene expression occurring in the brain after NSC treatment and may mediate functional recovery via activation of endogenous self-repair mechanisms, including oligodendrogenesis.

AN INDIRECT PATHWAY FOR GENETIC INFLUENCE ON THE FORMATION OF THE CEREBRAL PALSY PHENOTYPE: GENOME AND HYPOXIA TOLERANCE

2019 ◽  
Vol 25 (5-6) ◽  
pp. 328-334
Author(s):  
P. L Sokolov ◽  
A. G Prityko ◽  
Natal’ya V. Chebanenko ◽  
P. A.I Romanov
Keyword(s):  
Cerebral Palsy ◽  
Molecular Genetic ◽  
Fetal Brain ◽  
Scientific Data ◽  
Micro Rna ◽  
Hypoxia Tolerance ◽  
Control Mechanisms ◽  
Indirect Pathway ◽  
Gene Expression Control ◽  
Hypoxia Ischemia

The incidence of cerebral palsy is increasing. In 70% of cases, the disease develops as a result of exposure to known pathogenesis factors, such as hypoxia-ischemia, infectious, toxic, and traumatic damage to the fetus. In 30% of cases of the disease, the effect of pathogenetic factors is absent. This determines the relevance of the search for genetic anomalies responsible for the formation of this phenotype. Many genome disorders associated with the development of the cerebral palsy phenotype have been identified. Of particular interest is the indirect influence of genetic factors of pathogenesis, affecting the formation of the disease indirectly, through the mechanisms of formation of hypoxic-ischemic brain damage. Such factors affect almost all stages of the “ischemic cascade”: the formation of a “glutamate shock”, the realization of a “glutamate shock” by cytokines, the defect of the antioxidant defense of a neuron, the realization of the cytotoxic effect of nitric oxide (NO), and the stimulation of apoptosis of neurons and microglia. This makes it possible to identify genome variants that determine the tolerance of the child’s brain to hypoxic-ischemic damage. The combination of carriers of such anomalies into risk groups will make it possible to differentiate the tactics of their observation in the natal and postnatal periods in order to reduce the likelihood of the formation of severe hypoxic-ischemic lesions of the central nervous system and cerebral palsy. Today, a large amount of scientific data has been accumulated on the molecular genetic mechanisms of the pathogenesis of perinatal brain lesions. Such as epigenetic, transcriptome gene expression control mechanisms via micro-RNA. The available information allows us to experimentally develop new methods for protecting the fetal brain from hypoxia-ischemia and stopping the effects of hypoxia-ischemia in the neonatal period.

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