ORCID Profile
0000-0002-8159-5901
Current Organisation
Hudson Institute of Medical Research
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Publisher: Elsevier BV
Date: 05-2023
Publisher: Springer Science and Business Media LLC
Date: 04-08-2021
DOI: 10.1038/S41598-021-95035-1
Abstract: Preclinical and clinical studies have shown that sex is a significant risk factor for perinatal morbidity and mortality, with males being more susceptible to neonatal hypoxic ischemic (HI) brain injury. No study has investigated sexual dimorphism in the efficacy of umbilical cord blood (UCB) cell therapy. HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received 3 doses of UCB cells (PND11, 13, 20) and underwent behavioural testing. On PND50, brains were collected for immunohistochemical analysis. Behavioural and neuropathological outcomes were assessed for sex differences. HI brain injury resulted in a significant decrease in brain weight and increase in tissue loss in females and males. Females and males also exhibited significant cell death, region-specific neuron loss and long-term behavioural deficits. Females had significantly smaller brains overall compared to males and males had significantly reduced neuron numbers in the cortex compared to females. UCB administration improved multiple aspects of neuropathology and functional outcomes in males and females. Females and males both exhibited injury following HI. This is the first preclinical evidence that UCB is an appropriate treatment for neonatal brain injury in both female and male neonates.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2018
Publisher: MDPI AG
Date: 17-05-2019
DOI: 10.3390/IJMS20102449
Abstract: Cerebral palsy (CP) is a permanent motor disorder that results from brain injury and neuroinflammation during the perinatal period. Mesenchymal stromal cells (MSCs) have been explored as a therapy in multiple adult neuroinflammatory conditions. Our study examined the therapeutic benefits of intranasal delivery of human umbilical cord tissue (UC) derived-MSCs in a rat model of neonatal hypoxic–ischemic (HI) brain injury. To do this, HI was performed on postnatal day 10 Sprague-Dawley rat pups via permanent ligation of the left carotid artery, followed by a hypoxic challenge of 8% oxygen for 90 min. A total of 200,000 UC-MSCs (10 million/kg) were administered intranasally 24 h post-HI. Motor control was assessed after seven days, followed by post-mortem. Analysis included brain immunohistochemistry, gene analysis and serum cytokine measurement. Neonatal HI resulted in brain injury with significant loss of neurons, particularly in the hippoc us. Intranasal administration of UC-MSCs significantly reduced the loss of brain tissue and increased the number of hippoc al neurons. HI significantly upregulated brain inflammation and expression of pro-inflammatory cytokines, while intranasal UC-MSCs significantly reduced markers of neuroinflammation. This study demonstrated that a clinically relevant dose (10 million/kg) of UC-MSCs was neuroprotective following HI by restoring neuronal cell numbers and reducing brain inflammation. Therefore, intranasal delivery of UC-MSCs may be an effective therapy for neonatal brain injury.
Publisher: InTech
Date: 11-01-2017
DOI: 10.5772/66647
Publisher: Frontiers Media SA
Date: 22-03-2019
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1016/J.BBR.2021.113322
Abstract: Hypoxic ischemic (HI) brain injury is a significant cause of childhood neurological deficits. Preclinical rodent models are often used to study these deficits however, no preclinical study has determined which behavioral tests are most appropriate for long-term follow up after neonatal HI. HI brain injury was induced in postnatal day (PND) 10 rat pups using the Rice-Vannucci method of unilateral carotid artery ligation. Rats underwent long-term behavioral testing to assess motor and cognitive outcomes between PND11-50. Behavioral scores were transformed into Z-scores and combined to create composite behavioral scores. HI rats showed a significant deficit in three out of eight behavioral tests: negative geotaxis analysis, the cylinder test and the novel object recognition test. These in idual test outcomes were transformed into Z-scores and combined to create a composite Z-score. This composite z-score showed that HI rats had a significantly increased behavioral burden over the course of the experiment. In this study we have identified tests that highlight specific cognitive and motor deficits in a rat model of neonatal HI. Due to the high variability in this model of neonatal HI brain injury, significant impairment is not always observed in in idual behavioral tests, but by combining outcomes from these in idual tests, long-term behavioral burden can be measured.
No related grants have been discovered for Tayla Penny.