96625 Journal Article.pdf (243.23 kB)
Allopregnanolone and its precursor progesterone do not reduce injury after experimental stroke in hypertensive rats - Role of postoperative temperature regulation?
journal contribution
posted on 2023-05-18, 05:09 authored by Spratt, NJ, Tomkins, AJ, Pepperall, D, McLeod, DD, Calford, MBAllopregnanolone is a neurosteroid synthesized from progesterone in brain. It increases inhibition through modulation of the gamma-aminobutyric acid type A (GABA-A) receptor. Both agents are putative neuroprotectants after ischemic stroke. We sought to confirm their effectiveness in a hypertensive rat stroke model, with intra- and post-operative temperature regulation. The primary study compared allopregnanolone, progesterone or vehicle control treatments, administered 105 minutes after induction of temporary middle cerebral artery occlusion in spontaneously hypertensive rats. Temperature was controlled intraoperatively and a heat mat used in the 6 hours postoperatively to permit animal temperature self-regulation. The primary outcome was infarct volume and secondary outcomes were tests of sensory and motor function. There was no significant effect of treatment on any outcome measure. Given prior reports of GABA-A receptor agonists causing hypothermia, follow-up experiments were conducted to examine postoperative temperature regulation. These did not reveal a difference in postoperative temperature in neurosteroid-treated animals compared to control. However, in all rats maintained postoperatively in ambient temperature, moderate hypothermia was observed. This was in contrast to rats maintained over a heat mat. The lowest mean postoperative temperature was between 34.4-34.9°C in all 3 groups. These data do not support a neuroprotective effect of allopregnanolone or progesterone in ischemic stroke in hypertensives in the setting of normothermia. Given previous evidence of synergy between neuroprotective agents and hypothermia, demonstration of neuroprotective effect of these agents in the absence of postoperative hypothermia would be prudent before consideration of these agents for further clinical investigation.
History
Publication title
PLoS OneVolume
9Issue
9Article number
e107752Number
e107752Pagination
1-6ISSN
1932-6203Department/School
Tasmanian School of MedicinePublisher
Public Library of SciencePlace of publication
United StatesRights statement
Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/Repository Status
- Open