Administration of low dose estrogen attenuates gliosis and protects neurons in acute spinal cord injury in rats

Abstract

Spinal cord injury (SCI) is a debilitating condition with neurological deficits and loss of motor function that, depending on the severity, may lead to paralysis. The only treatment currently available is methylprednisolone, which is widely used and renders limited efficacy in SCI. Therefore, other therapeutic agents must be developed. The neuroprotective efficacy of estrogen in SCI was studied with a pre-clinical and pro-translational perspective. Acute SCI was induced in rats that were treated with low doses of estrogen (1, 5, 10, or 100 µg/kg) and compared with vehicle-treated injured rats or laminectomy control (sham) rats at 48 hours post-SCI. Changes in gliosis and other pro-inflammatory responses, expression and activity of proteolytic enzymes (e.g., calpain, caspase-3), apoptosis of neurons in SCI, and cell death were monitored via Western blot and immunohistochemistry. Negligible pro-inflammatory responses or proteolytic events and very low levels of neuronal death were found in sham rats. In contrast, vehicle-treated SCI rats showed profound pro-inflammatory responses with reactive gliosis, elevated expression and activity of calpain and caspase-3, elevated Bax:Bcl2 ratio, and high levels of neuronal death in lesion and caudal regions of the injured spinal cord. Estrogen treatment at each dose reduced pro-inflammatory and proteolytic activities and protected neurons in the caudal penumbra in acute SCI. Estrogen treatment at 10 µg was found to be as effective as 100 µg in ameliorating the above parameters in injured animals. Results from this investigation indicated that estrogen at a low dose may be a promising therapeutic agent for treating acute SCI.

Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats

“…; Samantaray et al . ), further experiments were performed to determine if microgliosis and astrogliosis remained inhibited following chronic SCI (day 42). In the current investigation, rats did not receive estrogen therapy beyond 7 days post‐SCI.…”

“…The attenuation of these destructive pathways by very low doses of estrogen in acute SCI (Samantaray et al . ) suggests its neuroprotective capability in ameliorating dysfunction in long‐term (chronic) SCI as well as estrogen's potential as a therapy in human SCI.…”

“…The current studies on the efficacy of low dose estrogen (10 lg/kg) in a chronic SCI rat model assessing recovery of function were investigated on the basis of findings described in more detail in a preceding manuscript (Samantaray et al 2015). The estrogen-mediated attenuation of many different destructive parameters that are involved in the degenerative process in acute injury suggests that its efficacy may be tested in the chronic, long-term SCI.…”

Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats

“…against secondary SCI, together with neuroregenerative agents (e.g., gangliosides, Rho antagonist, anti-Nogo antibodies, acidic fibroblast growth factor) have been used in SCI (Table I) with mixed outcomes (28–39). Recent studies also evaluated the potential beneficial effects of estrogen, which could be a neuroprotective agent in the treatment of SCI and TBI (40–43). Using a novel strategy of nanoparticle delivery of estrogen showed promising results with induction of anti-Inflammatory effects after SCI in rats (44).…”

Therapeutic Effect of Curcumin and Methylprednisolone in the Rat Spinal Cord Injury

“…The development of therapeutic approaches for SCI as of yet still remains a problem to researchers and scientists alike (Raspa et al, ). As such, the sagacity of new therapeutics with maximal capacity to improve sensory and motor function after SCI is of utmost importance (Samantaray et al, ). Several studies using renovate strategies have indicated that damaged axons can be regenerated through the lesion site when given an appropriate environment (Zeng et al, ).…”