Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats

Abstract

Spinal cord injury (SCI) leads to neurological deficit and motor dysfunction. Methylprednisolone, the only drug used for treating SCI, renders limited neuroprotection and remains controversial. Estrogen is one of the most potent multi-active neuroprotective agents and it is currently under investigation in our laboratory for its efficacy in SCI. The present review briefly summarizes our earlier findings on the therapeutic potential of pharmacological/supraphysiological levels of estrogen in SCI and outlines our ongoing research, highlighting the efficacy of physiological levels of estrogen against neuronal injury, axonal degeneration, and gliosis and also the molecular mechanisms of such neuroprotection in experimental SCI. Furthermore, our ongoing studies designed to explore the different translational potential of estrogen therapy suggest that this multi-active steroid may act as an adjunct therapy to promote angiogenesis, thus enhancing the functional recovery following chronic SCI. Taken together, these studies confirm that estrogen is a potential therapeutic agent for treating SCI.

Spinal Cord Injury: A Review of Current Therapy, Future Treatments, and Basic Science Frontiers

“…In particular, a variety of therapies have been studied to alter neuro-inflammation [1, 12–14], reduce free radical damage[15–17], reduce excitotoxic damage to neurons [18, 19], improve blood flow [20, 21], and counter the effects of local ionic changes [21–25]. Previous investigations from our laboratories indicated increased intracellular free Ca 2+ levels, increased proteolytic activity, degradation of myelin and cytoskeletal proteins, granular degeneration of axons, and vesiculation of myelin all of which contribute to secondary injury and propagation of SCI [12, 17, 26– 28]. …”

Crosstalk Between the Immune and Central Nervous Systems with Special Reference to Drug Development

“…Along with this concept, anti-inflammatory steroids and immunosuppressive therapeutic interventions are currently used to treat autoimmune neurological diseases and brain/spinal cord injuries. However, these therapies have limited clinical benefits while showing severe side effects (Kim Y et al, 2009;Barten LJ et al, 2010;Hilas O et al, 2010;Samantaray S et al, 2010). In contrast, several evidences have demonstrated that the immune cells rather have beneficial impacts on the pathology of the CNS diseases (WyssCoray T & Mucke L, 2002;Donnelly DJ & Popovich PG, 2008).…”

G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury*

“…Furthermore, a series of studies has shown that estrogen has beneficial effects in a variety of models of neurological diseases including SCI (8,14,15). Classically, the broad spectrum of estrogenic biological effects is believed to be mediated by two forms of nuclear estrogen receptor (ERα and ERβ) by regulating gene transcription (16,17).…”

“…Although considerable advances have been made in SCI therapy (1,7), no therapeutic agent has proven effective in restoring the motor functions of patients so far. Consequently, there is an imperative need or development of efficient drugs for the treatment of SCI (8,9).…”