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Progesterone and low-dose vitamin D hormone treatment enhances sparing of memory following traumatic brain injury.
- Source :
-
Hormones and behavior [Horm Behav] 2012 Apr; Vol. 61 (4), pp. 642-51. - Publication Year :
- 2012
-
Abstract
- Progesterone (PROG) has been shown to protect the brain from traumatic injury and is now in Phase III clinical trials. Our work shows that PROG's beneficial effects can be reduced in vitamin D hormone (VDH)-deficient subjects. VDH can modulate neuronal apoptosis, trophic factors, inflammation, oxidative stress, excitotoxicity, and myelin and axon repair. We investigated whether VDH combined with PROG could improve behavioral outcomes more than PROG alone in VDH-sufficient rats given bilateral contusions of the medial frontal cortex. PROG and different doses of VDH (1 μg/kg, VDH1; 2.5 μg/kg, VDH2; 5 μg/kg, VDH3) were injected intraperitoneally 1 h post-injury. Eight additional doses of PROG were given subcutaneously over 8 days with tapering over the last 2 days. Neurobehavioral tests, necrotic cavity, neuronal death and activation of astrocytes were evaluated 21 days post-injury. We found that PROG and PROG + VDH preserve spatial memory processing. VDH1 + PROG improved performance in acquisition more effectively than PROG alone, indicating that the low VDH dose is optimal for combination therapy. There were no significant differences in necrotic cavity size among the groups. The density of positive staining for reactive astrocytes (glial fibrillary acidic protein (GFAP)) increased and the cell bodies and processes of GFAP-positive cells were enlarged in the PROG + VDH1 group. Our data indicate that the combination of PROG and VDH is more effective than PROG alone in preserving spatial and reference memory, and that PROG plus low-dose VDH can activateGFAP reactions up to 21 days after injury. This effect may be one of the mechanisms underlying PROG's neuroprotective effects in combination with VDH.
- Subjects :
- Animals
Astrocytes drug effects
Astrocytes pathology
Behavior, Animal drug effects
Body Weight drug effects
Brain Injuries psychology
Cell Death drug effects
Dose-Response Relationship, Drug
Fluoresceins
Fluorescent Dyes
Frontal Lobe injuries
Frontal Lobe pathology
Glial Fibrillary Acidic Protein metabolism
Immunohistochemistry
Male
Maze Learning drug effects
Memory Disorders psychology
Motor Activity drug effects
Necrosis
Neurons drug effects
Neurons pathology
Progesterone administration & dosage
Psychomotor Performance drug effects
Psychomotor Performance physiology
Rats
Rats, Sprague-Dawley
Sensation Disorders etiology
Sensation Disorders prevention & control
Survival
Vitamin D administration & dosage
Vitamins administration & dosage
Brain Injuries complications
Memory Disorders etiology
Memory Disorders prevention & control
Neuroprotective Agents
Progesterone pharmacology
Vitamin D pharmacology
Vitamins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6867
- Volume :
- 61
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Hormones and behavior
- Publication Type :
- Academic Journal
- Accession number :
- 22570859
- Full Text :
- https://doi.org/10.1016/j.yhbeh.2012.02.017