Introduction

An initial study showed that pseudopregnant females (with

high circulating levels of progesterone) developed almost no
postinjury brain edema after TBI
Carswell et al reported that brain injury outcomes are
improved in proestrus stage compared to the non-proestrus
stages of estrous cycle
Implication of NMU and NMS in stress, inflammation, and a
variety of autonomic and neuroendocrine functions,
protective role in the setting of neurodegenerative disease.
CS: Effects of the administration of physiologic doses of 17β-
estradiol and progesterone on cerebral edema, NMS, NMU,
and NMUR2 mRNA expression in ovariectomized female rats
following traumatic brain injury
Materials and Methods
Experimental protocols
Bilateral ovariectomy and capsule implantation
Preparation of the capsules
Determination of estrous cycle
Hormone analysis
Induction of TBI
Brain edema assessment
Measurement of brain NMU content
RNA extraction and cDNA synthesis
Real-time PCR quantification
Extraction of protein
Results
Brain Edema
Serum Hormone Measurements
Immunoblot Analysis
Discussion
1. Prepro-NMS
TBI-HP>TBI-HE (relatif)

2. NMU
LP-E> OVX

LP-E> untreated group

3. mRNA NMUR2
Upregulated in TBI-HP and LP-treated rats respect to
corresponding groups treated by different doses of 17β-estradiol
• NMUR2 significantly decreased in animals following ovariectomy
• Yang et al : expression of NMS mRNA and NMUR2 were highest in the
proestrus stage in hypothalamus and pituitary of the pigs.
• The activity of NMS is about 10x stronger than that of the NMU, NMS >
important in the brain
• The rat NMUR2 gene is mostly expressed in the specific regions : 1)
ependymal layer along the wall of the third ventricle (role of edema
formation). 2) brain structures which lack a blood-brain barrier (BBB)
such as subfornical organ, vascular organ of the lamina terminalis.
• Expression pattern of the NMUR2 gene in the regions in contact with the
cerebrospinal fluid.
• Lipid peroxidation + free radical production -> BBB permeability +
edema formation
• Progesteron  lipid peroxidation
• Intraventricular injection (NMS)  oxidative stress
• NMS  lipid perox & brain tissue damage
• Estrogen receptors α and β  proinflammation cytokine , anti-
inflammation cytokine, superoxide dismutase activity
• Progesteron  vasopressin  water balance regulation
Neuroinflam Hippocampus
Lipopolisaccharide
mation BDNF

Degranulation of mast
cell (monocyte, dendrit
cell, B cell)

Downregulation

Edema COX2 NMU

Formation ROS
NOS

Antiinflammation
Conclusion
Progesterone administration increased prepro-NMS and
NMUR2 expression which were concurrent with its
protective effect in traumatic animals
It is likely that such changes are involved in the induction
of neuroprotective effects of progesterone.