title: Progesterone Exacerbates Short-Term Effects of Traumatic Brain Injury on Supragranular Responses in Sensory Cortex and Over-Excites Infragranular Responses in the Long Term.
abstract: Progesterone (P4) has been suggested as a neuroprotective agent for traumatic brain injury (TBI) because it ameliorates many post-TBI sequelae. We examined the effects of P4 treatment on the short-term (4 days post-TBI) and long-term (8 weeks post-TBI) aftermath on neuronal processing in the rodent sensory cortex of impact acceleration-induced diffuse TBI. We have previously reported that in sensory cortex, diffuse TBI induces a short-term hypoexcitation that is greatest in the supragranular layers and decreases with depth, but a long-term hyperexcitation that is exclusive to the supragranular layers. Now, adult male TBI-treated rats administered P4 showed, in the short term, even greater suppression in neural responses in supragranular layers but a reversal of the TBI-induced suppression in granular and infragranular layers. In long-term TBI there were only inconsistent effects of P4 on the TBI-induced hyperexcitation in supragranular responses but infragranular responses, which were not affected by TBI alone, were elevated by P4 treatment. Intriguingly, the effects in the injured brain were almost identical to P4 effects in the normal brain, as seen in sham control animals treated with P4: in the short term, P4 effects in the normal brain were identical to those exercised in the injured brain and in the long term, P4 effects in the normal brain were rather similar to what was seen in the TBI brain. Overall, these results provide no support for any protective effects of P4 treatment on neuronal encoding in diffuse TBI, and this was reflected in sensorimotor and other behavior tasks also tested here. Additionally, the effects suggest that mechanisms used for P4 effects in the normal brain are also intact in the injured brain.
authors.affiliation: 1 Department of Physiology, Monash University , Clayton VIC, Australia .
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Allitt
authors.affiliation: 1 Department of Physiology, Monash University , Clayton VIC, Australia .|2 Current address: School of Anatomy, Physiology & Human Biology, The University of Western Australia , Crawley WA, Australia .
authors.forename: Victoria P A
authors.initials: VP
authors.lastname: Johnstone
authors.affiliation: 1 Department of Physiology, Monash University , Clayton VIC, Australia .
authors.forename: Katrina
authors.initials: K
authors.lastname: Richards
authors.affiliation: 1 Department of Physiology, Monash University , Clayton VIC, Australia .
authors.forename: Edwin B
authors.initials: EB
authors.lastname: Yan
authors.affiliation: 1 Department of Physiology, Monash University , Clayton VIC, Australia .
authors.forename: Ramesh
authors.initials: R
authors.lastname: Rajan
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D011374:Progesterone
keywords: diffuse TBI; electrophysiology; neuronal encoding; progesterone; sensory cortex