Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury

Abstract

In recent years there has been a growing body of clinical and laboratory evidence demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury (TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory studies have demonstrated that estrogen and progesterone administration is associated with a mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity. Future laboratory research is needed to better determine the mechanisms underlying the hormones’ neuroprotective effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to better assess their role in human neurodegenerative conditions.

An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period

“…In general, the activity of hormonal signaling through their receptors can suppress the transcriptional regulation of inflammatory cytokines (Robinson and Klein, 2012). For example, progesterone has been found to be anti-inflammatory in the face of an ischemic challenge, nerve damage, or even infection (Brotfain et al, 2016; Kipp et al, 2016; Labombarda et al, 2015; Lammerding et al, 2016; Paris et al, 2016; Perez-Alvarez and Wandosell, 2016). Additionally, during lactation, progesterone contributes to an increase in astrocytes in the rodent cingulate cortex (Salmaso et al, 2009) and the dentate gyrus of the hippocampus (Cabrera et al, 2013).…”

Chronic Oral Administration of Tenebrio molitor Extract Exhibits Inhibitory Effect on Glucocorticoid Receptor Overexpression in the Hippocampus of Ovariectomy‐Induced Estrogen Deficient Mice

“…In other words, the glucocorticoid receptor (GR) is known as a main marker describing the regulatory mechanism of HPA axis and will be used a basis for determining the change in HPA axis regulation by estrogen deficiency in the present study. GR, cell proliferation (Ki67), and neuroblast (DCX) expression levels in estrogen deficient and neurodegenerative dysfunction animal models have been reported in previous studies (Agca et al., ; Anukulthanakorn et al., ; Brotfain et al., ; Fowler, Liu, & Wang, ; Fuxe et al., ; Gordon et al., ; Krishnamurthy et al., ; Shao, Cheng, & Jin, ; Zhao et al., ).…”

“…. . and neuroblast (DCX) expression levels in estrogen deficient and neurodegenerative dysfunction animal models have been reported in previous studies (Agca et al, 2008;Anukulthanakorn et al, 2016;Brotfain et al, 2016;Fowler, Liu, & Wang, 2008;Fuxe et al, 1987;Gordon et al, 2015;Krishnamurthy et al, 2008;Shao, Cheng, & Jin, 2012;Zhao et al, 2015).…”

Cellular and Molecular Mechanisms of the Effects of Sex Hormones on the Nervous System

“…Other mechanisms implicated here may include the anti-inflammatory effect associated with suppression of microglia, inflammatory cytokines, and free radicals production, which cause inflammatory damage to the neurons, effects on endothelial cells realized by increasing the mitochondrial efficiency and stimulating angiogenesis, genomic influence on anti-apoptotic protein genes of Bcl family and reduction of apoptotic trends and effect of free radical scavenging. These are the hypothetical models of estrogen neuroprotection in cerebral ischemia and in other neurodegenerative disorders such as Parkinson's disease (PD) and AD [52,56].…”

“…Progesterone stimulates the neurological and functional recovery after spinal and brain traumas [56,69] and exerts neuroprotection in cerebral ischemia [70,71].…”