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

Samantaray, Supriti; Das, Arabinda; Matzelle, Denise; Yu, Shan Ping; Wei, Ling; Varma, Abhay K.; Ray, Swapan K.; Banik, Naren L.

doi:10.1111/jnc.13610

Cited by 48 publications

(45 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The neuroprotective effect of estrogen was mainly due to decrease in Caspase-3 activity, which was accompanied by a reduction of motor neuron death following injury ( Cuzzocrea et al, 2008 and Kachadroka et al, 2010) and inhibition of N-methyl-D-aspartic acid (NMDA) receptors (subtype of glutamate receptor) that are ordinarily activated following KA injection (Weaver et al, 1997). Our results also agree with the results of previous studies which revealed that the edema and degenerated ventral horn neurons were noticeably attenuated in estrogen treated groups compared to vehicle-treated lesion (Sribnick et al, 2005, 2010 , Siriphorn et al, 2012 and Samantaray et al, 2016) .…”

Section: Discussionsupporting

confidence: 93%

“…Thus combining complementary strategies would be required to advance stem cells-based treatments to the clinical stage (Teng et al, 2002) . In the current study, to further enhance the survival, proliferation and migration of transplanted adult OBNSCs in the hostile microenvironment of SCI, we treated the animals with estrogen as neuroprotective, immunomodulatory and anti-inflammatory agent (Siriphorn et al, 2012 and samantaray et al, 2016.) This was done rapidly after KA injury to prevent the acceleration of primary and secondary tissue damage and to prevent microglial invasion to the injured cord.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

Marei

Althani

Abd‐Elmaksoud

et al. 2019

Preprint

View full text Add to dashboard Cite

In the present study we developed an excitotoxic spinal cord injury (SCI) model using kainic acid (KA) to evaluate of the therapeutic potential of human olfactory bulb neural stem cells (h-OBNSCs) for spinal cord injury (SCI). In a previous study, we assessed the therapeutic potential of these cells for SCI; all transplanted animals showed successful engraftment. These cells differentiated predominantly as astrocytes, not motor neurons, so no improvement in motor functions was detected. In the current study we used estrogen as neuroprotective therapy before transplantation of OBNSCs to preserve some of endogenous neurons and enhance the differentiation of these cells towards neurons. The present work demonstrated that the h-GFP-OBNSCs were able to survive for more than eight weeks after sub-acute transplantation into injured spinal cord. Stereological quantification of OBNSCs showed approximately a 2.38-fold increase in the initial cell population transplanted. 40.91% of OBNSCs showed differentiation along the neuronal lineages, which was the predominant fate of these cells. 36.36% of the cells differentiated into mature astrocytes; meanwhile 22.73% of the cells differentiated into oligodendrocytes. Improvement in motor functions was also detected after cell transplantation.Spinal cord injury (SCI) is any damage to the spinal cord leading to a change, either temporary or permanent, in the normal motor, sensory and autonomic function of the cord. Globally over 20 million individuals suffer from paralysis caused by SCI (Lee et al., 2014). The number of SCI patients is continually increasing, and each year, an estimated 180,000 individuals over the world get a new injury (Lee et al., 2014). The severity of injury and its location on the spinal cord determine the symptoms of SCI. Symptoms may vary from partial to complete loss of sensory and motor function of the arms, legs and/or body. Disturbance of breathing, heart rate, blood pressure, bowel or bladder controls are considered the most severe forms of the injury (Yılmaz et al. 2014). The main causes of SCI are motor vehicle accidents, acts of violence, sports injuries, and some diseases such as osteoporosis, arthritis and cancer of the spinal cord (Bellucci et al., 2015 and McCaughey et al., 2016). The pathophysiology of spinal cord injury is best described as bi-phasic, involving both a primary (cause of injury) and secondary phase. The primary phase of injury followed by rapid and progressive secondary injury events include physiological, anatomical and neurochemical changes leading to permanent neuronal cell death and glial scar and syrinx formation (Choo et al., 2007). Various models of SCI are based on surgical methods, which are determined by the aims of the particular research (Akhtar et al., 2008). In this study the KA was used to induce an excitotoxic SCI model. The induction of KA as a very effective excitotoxin was first done by Olney, (1974). KA has been widely utilized as a specific agonist for ionotropic glutamate receptors (iGluRs) to mimic the effe...

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

Marei

Althani

Abd‐Elmaksoud

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The most serious result of SCI is caused by secondary injury, resulted in a mass of cell death [27][28][29][30]. After SCT, NeuN expression was significantly down-regulated and NeuN has been used as a marker of neuron to indicate that neuronal death emerged in SCT.…”

Section: Bdnf Overexpression Promoted Neuronal Survival and Axonal Rementioning

confidence: 99%

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

et al. 2016

View full text Add to dashboard Cite

Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

show abstract

“…Different low doses and times of administration (between 10 and 100 μg/ kg/day/7 days to 4 mg/kg/15 min and 24 h, i.v.) appear to be effective, suggesting that pre-treatment or immediate posttreatment at either physiological or supraphysiological dose could minimize secondary injury in SCI and promote functional recovery, reflected in both acute and chronic stages [44,45]. Additionally, the development of selective agonists of ER with higher affinity for ERα, ERβ, or both, such as tamoxifen, looks promising in SCI treatment, when applied in subdermal implants 7 days before, immediately, or 24 h post-injury; with an immediate release of 0.71 mg/day for 21 days, it provided motor recovery and preservation of white matter, dorsal and ventral horn neurons, with a decrease of O 2…”

Section: Estrogenmentioning

confidence: 99%

Current Developments in Antioxidant Therapies for Spinal Cord Injury

Villa¹,

Villamar²,

Zapien³

et al. 2019

Spinal Cord Injury Therapy [Working Title]

View full text Add to dashboard Cite

When spinal cord injury (SCI) occurs, numerous sources of reactive oxygen species and nitrogen species may be active within first minutes or hours and even reactivate few days later. Free radical formation and lipid peroxidation (LP) have been described as an important mechanism in the beginning and accelerated progress in the development of diverse pathologies, importantly in those related to central nervous system. The compromise of molecules and cellular structures due to the oxidative state of microenvironment in SCI may determinate survival or apoptosis of resident and infiltrating cells and polarization toward an inflammatory response, which lead to an extension of damaged tissue and loss of neuronal function, or a regulatory/regenerative response. The investigation of new antioxidant agents and their action at a molecular level begins to reveal mechanisms that, if correctly modulated, promise an improvement in recovery of functions with respect to conventional pharmacological therapies. In this chapter, we will review the general mechanisms of oxidative stress and lipid peroxidation, those antioxidant treatments in experimental development and clinical phase, as well as their achievements and limitations.

show abstract

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

Cited by 48 publications

References 77 publications

Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

Current Developments in Antioxidant Therapies for Spinal Cord Injury

Contact Info

Product

Resources

About