Progesterone: therapeutic opportunities for neuroprotection and myelin repair

[Guest guest]

Pharmacol Ther. 2007 Oct;116(1):77-106.

Progesterone: therapeutic opportunities for neuroprotection and

myelin repair.

Schumacher M, Guennoun R, Stein DG, De Nicola AF.

UMR 788 Inserm and University Paris-Sud 11, Kremlin-Bicêtre, France.

Progesterone and its metabolites promote the viability of neurons in

the brain and spinal cord. Their neuroprotective effects have been

documented in different lesion models, including traumatic brain

injury (TBI), experimentally induced ischemia, spinal cord lesions

and a genetic model of motoneuron disease. Progesterone plays an

important role in developmental myelination and in myelin repair, and

the aging nervous system appears to remain sensitive to some of

progesterone's beneficial effects. Thus, the hormone may promote

neuroregeneration by several different actions by reducing

inflammation, swelling and apoptosis, thereby increasing the survival

of neurons, and by promoting the formation of new myelin sheaths.

Recognition of the important pleiotropic effects of progesterone

opens novel perspectives for the treatment of brain lesions and

diseases of the nervous system. Over the last decade, there have been

a growing number of studies showing that exogenous administration of

progesterone or some of its metabolites can be successfully used to

treat traumatic brain and spinal cord injury, as well as ischemic

stroke. Progesterone can also be synthesized by neurons and by glial

cells within the nervous system. This finding opens the way for a

promising therapeutic strategy, the use of pharmacological agents,

such as ligands of the translocator protein (18 kDa) (TSPO; the

former peripheral benzodiazepine receptor or PBR), to locally

increase the synthesis of steroids with neuroprotective and

neuroregenerative properties. A concept is emerging that progesterone

may exert different actions and use different signaling mechanisms in

normal and injured neural tissue.