Tayla R Penny1, Yen Pham2, Amy E Sutherland2, Jamie G Mihelakis2, Joohyung Lee3, Graham Jenkin1, Michael C Fahey4, Suzanne L Miller1, Courtney A McDonald5. 1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia. 2. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia. 3. Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Australia. 4. Department of Paediatrics, Monash University, Clayton, Victoria, Australia. 5. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia. Electronic address: Courtney.mcdonald@hudson.org.au.
Abstract
BACKGROUND: Hypoxic ischemic (HI) insults during pregnancy and birth can result in neurodevelopmental disorders, such as cerebral palsy. We have previously shown that a single dose of umbilical cord blood (UCB) cells is effective at reducing short-term neuroinflammation and improves short and long-term behavioural outcomes in rat pups. A single dose of UCB was not able to modulate long-term neuroinflammation or brain tissue loss. In this study we examined whether multiple doses of UCB can modulate neuroinflammation, decrease cerebral tissue damage and improve behavioural outcomes when followed up long-term. METHODS: HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received either 1 dose (PND11), or 3 doses (PND11, 13, 20) of UCB cells. Rats were followed with behavioural testing, to assess both motor and cognitive outcomes. On PND50, brains were collected for analysis. RESULTS: HI brain injury in rat pups caused significant behavioural deficits. These deficits were significantly improved by multiple doses of UCB. HI injury resulted in a significant decrease in brain weight and left hemisphere tissue, which was improved by multiple doses of UCB. HI resulted in increased cerebral apoptosis, loss of neurons and upregulation of activated microglia. Multiple doses of UCB modulated these neuropathologies. A single dose of UCB at PND11 did not improve behavioural or neuropathological outcomes. CONCLUSIONS: Treatment with repeated doses of UCB is more effective than a single dose for reducing tissue damage, improving brain pathology and restoring behavioural deficits following perinatal brain injury.
BACKGROUND:Hypoxic ischemic (HI) insults during pregnancy and birth can result in neurodevelopmental disorders, such as cerebral palsy. We have previously shown that a single dose of umbilical cord blood (UCB) cells is effective at reducing short-term neuroinflammation and improves short and long-term behavioural outcomes in rat pups. A single dose of UCB was not able to modulate long-term neuroinflammation or brain tissue loss. In this study we examined whether multiple doses of UCB can modulate neuroinflammation, decrease cerebral tissue damage and improve behavioural outcomes when followed up long-term. METHODS:HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received either 1 dose (PND11), or 3 doses (PND11, 13, 20) of UCB cells. Rats were followed with behavioural testing, to assess both motor and cognitive outcomes. On PND50, brains were collected for analysis. RESULTS:HI brain injury in rat pups caused significant behavioural deficits. These deficits were significantly improved by multiple doses of UCB. HI injury resulted in a significant decrease in brain weight and left hemisphere tissue, which was improved by multiple doses of UCB. HI resulted in increased cerebral apoptosis, loss of neurons and upregulation of activated microglia. Multiple doses of UCB modulated these neuropathologies. A single dose of UCB at PND11 did not improve behavioural or neuropathological outcomes. CONCLUSIONS: Treatment with repeated doses of UCB is more effective than a single dose for reducing tissue damage, improving brain pathology and restoring behavioural deficits following perinatal brain injury.
Authors: Joanne O Davidson; Lotte G van den Heuij; Simerdeep K Dhillon; Suzanne L Miller; Rebecca Lim; Graham Jenkin; Alistair J Gunn; Laura Bennet Journal: Int J Mol Sci Date: 2022-07-29 Impact factor: 6.208
Authors: Tayla R Penny; Yen Pham; Amy E Sutherland; Joohyung Lee; Graham Jenkin; Michael C Fahey; Suzanne L Miller; Courtney A McDonald Journal: Sci Rep Date: 2021-08-04 Impact factor: 4.379
Authors: Ashalyn P Watt; Mark Kirkland; Lakshmi Nekkanti; Yen Pham; Courtney McDonald; Atul Malhotra; Guy Moeneclaey; Suzanne L Miller; Graham Jenkin Journal: Cell Tissue Res Date: 2022-02-02 Impact factor: 5.249