Dr Jonathan Hirst BSc (Adelaide) PhD (Monash)
Contact Details
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Senior
Lecturer
Fetal and
Neonatal Research Group Postal Address. |
.........61 (0) 249 217965
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Current Research
Role of neurosteroid production in protecting against brain damage in the newborn and the contribution of adrenal products in maintaining neurosteroid synthesis.
Complications during pregnancy or at birth may lead to episodes of asphyxia and can result in neurological impairment in the newborn. The consequent brain injury may lead to life-long handicaps such as cerebral palsy. The placenta secretes a number of products that aid in protecting the fetal and newborn brain against asphyxia-induced damage. After birth the adrenal glands take over from the placenta in providing protection against stressful events. Preterm neonates often suffer from adrenal insufficiency or have suppressed adrenal function and therefore may be particularly vulnerable to brain damage. We are currently examining the expression reductase enzymes that produce protective steroids. The studies will also examine adrenal steroids levels in umbilical cord blood samples to determine the contribution of potentially protective adrenal products to reducing brain injury. These data should indicate if adrenal function is inadequate in these premature babies and if adrenal production is suppressed by certain maternal therapies.
The goal of these studies is to delineate strategies for maximizing neuroprotection in ‘at risk’ neonates and to identify the best therapeutic approaches for that maintaining steroid-mediated protection following complications during pregnancy.
Our hypothesis is: That suppression of adrenal steroidogenesis in the newborn lowers neurosteroid levels in the brain and increases vulnerability to brain injury following compromised pregnancy. Also that exogenous glucocorticoid administration will suppress adrenal neurosteroid precursor synthesis and reduce protective steroid production in the newborn brain.
The specific aims are:
To determine if neurosteroids protect the brain from stressful events at birth, and if deficiencies in steroid levels in babies increase their vulnerability to brain damage.
To determine if suppression of adrenal function reduces neurosteroid precursor availability and if this suppression increases cell death in the newborn brain.
Selected Publications
Olson, D. M, Zaragoza D. B., Shallow, M. C., Cook, J. L., Mitchell, B. F., Grigsby, P. L., Hirst, J. J. 2003 Myometrial activation and preterm labour: evidence supporting a role for the myometrial F receptor. Placenta 24 (Supplement: A): S47-S54.
Nguyen P. N., Billiards S.B., Walker, D. W., Hirst, J.J. 2003 Changes in 5a-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal brain. Pediatr. Res. 53:956-964
Crossley, K. J., Nitsos I., Walker, D.W., Lawrence A. J., Beart, P.M., Hirst J. J. 2003 Steroid-sensitive GABAA receptors in the fetal and neonatal brain. Neuropharmacology 45:461-472.
Nguyen P. N., Billiards, S. S, Walker, D. W., Hirst, J.J. 2003 Changes in 5a-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolisation. Pediatr. Res. 54:840-847.
Palliser, H.K., Dellios, N., Escalona, R., Ooi, G., Rice, G.E., Hirst, J.J., Young, I.R. 2004 prostaglandin synthetic enzymes in the ovine myometrium, endometrium and placenta during induced-preterm and spontaneous. J. Endocrinol 180: 469-477
Nguyen, P. N., Young, I.R., Walker, D. W., Hirst, J.J. 2004 Neurosteroids in the brain and blood after disruption of the hypothalamo –pituitary-adrenal axis in fetal sheep. J Endocrinal. 182: 81-88.
Nguyen, P. N., Yan, E. B., Castillo-melendez, M., Walker, D. W., Hirst, J. J. 2004 Increased allopregnanolone concentrations in the fetal brain following umbilical cord occlusion. J. Physiol. 560 Part 2: 593-602
Hirst, J. J. Parkington, H. C., Young, I.R., Palliser, H.K., Peri, K.G., Olson, D. M. 2005 Delay of preterm birth by THG113.31, a prostaglandin F2? receptor antagonist. Am J Obstet Gynecol 193: 256-266.
Palliser, H.K., Hirst, J.J., Ooi, G.T., Rice, G.E., Escalona, R.M., Dellios, N.L., Parkington, HC., Young, I.R. 2005 Prostaglandin E and F receptor expression and myometrial sensitivity at labour onset in sheep. Biol Reprod. 72:937-943
Palliser, H.K., Dellios, N., Escalona, R., Ooi, G., Rice, G.E., Hirst, J.J., Young, I.R. 2006 Changes in prostaglandin receptor expression in the amnion and cervix following preterm and spontaneous term labour. J Soc Gynecol Invest 13:19-24, 2006
Billiards, S. S., Nguyen, P. N., Canny, B. J., Walker, D. W., Hirst, J.J. 2006 Hypoxia and endotoxin interact to regulate sleep and allopregnanolone concentrations in the newborn lambs. Biol Neonate (in press; 28 Feb 06).
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.......61 (0) 249 217903
