Abstract:Findings of this study suggest that progesterone may be neuroprotective in patients with DAI. However, large clinical trials are needed to assess progesterone as a promising drug in DAI.
AbstractIn recent years, the use of mesenchymal stem cells as a novel approach in the treatment of neurodegenerative diseases including traumatic brain injury has been proposed. In this study, the effect of oral mucosal mesenchymal stem cells (OMSCs) on traumatic brain injury was evaluated in long-term. Animals were divided into 4 groups including sham, TBI, vehicle (Veh) and stem cell (SC). Brain damage was induced by the Marmarou’s method. The number of 2 × 106 OMSCs was intravenously injected 1 and 24 hours after the injury. Brain edema and pathological outcome were assessed at 24 hours and 21 days after the injury. Besides, long-term neurological, motor and cognitive outcomes were evaluated at days 3, 7, 14, and 21 after the injury. inflammation (P < 0.01), reduce axonal damage (P < 0.01, P < 0.05; respectively) and prevent microglia proliferation (P < 0.05, P < 0.01; respectively) at 24 h and 21 days after the injury. Neurological function improvement (P < 0.001), memory enhancement (P < 0.05), anxiety-like behavior reduction (P < 0.001) and motor function amelioration (P < 0.05, P < 0.001, P < 0.01, P < 0.05; respectively) at days of 3, 7, 14, 21 after the injury were observed in the treatment group. According to the results of this study, OMSCs administration after TBI reduced brain edema and inflammation, and improved neurologic, memory and motor impairments, and anxiety-like behavior in long-term. Therefore, OMSCs could be a promising and new treatment option for TBI in the future.
AbstractIn recent years, the use of mesenchymal stem cells as a novel approach in the treatment of neurodegenerative diseases including traumatic brain injury has been proposed. In this study, the effect of oral mucosal mesenchymal stem cells (OMSCs) on traumatic brain injury was evaluated in long-term. Animals were divided into 4 groups including sham, TBI, vehicle (Veh) and stem cell (SC). Brain damage was induced by the Marmarou’s method. The number of 2 × 106 OMSCs was intravenously injected 1 and 24 hours after the injury. Brain edema and pathological outcome were assessed at 24 hours and 21 days after the injury. Besides, long-term neurological, motor and cognitive outcomes were evaluated at days 3, 7, 14, and 21 after the injury. inflammation (P < 0.01), reduce axonal damage (P < 0.01, P < 0.05; respectively) and prevent microglia proliferation (P < 0.05, P < 0.01; respectively) at 24 h and 21 days after the injury. Neurological function improvement (P < 0.001), memory enhancement (P < 0.05), anxiety-like behavior reduction (P < 0.001) and motor function amelioration (P < 0.05, P < 0.001, P < 0.01, P < 0.05; respectively) at days of 3, 7, 14, 21 after the injury were observed in the treatment group. According to the results of this study, OMSCs administration after TBI reduced brain edema and inflammation, and improved neurologic, memory and motor impairments, and anxiety-like behavior in long-term. Therefore, OMSCs could be a promising and new treatment option for TBI in the future.
“…As shown in Fig. 2 , three studies showed a significant individual RR (p < 0.05) favoring the treatment group 32 , 34 , 37 . Figure 2 Meta-analysis including 15 studies evaluating the effect of drugs with anti-inflammatory properties on a favorable outcome in TBI patients.…”
Section: Resultsmentioning
confidence: 82%
“…As shown in Fig. 2, three studies showed a significant individual RR (p < 0.05) favoring the treatment group 32,34,37 .…”
Outcome after traumatic brain injury (TBI) varies largely and degree of immune activation is an important determinant factor. This meta-analysis evaluates the efficacy of drugs with anti-inflammatory properties in improving neurological and functional outcome. The systematic search following PRISMA guidelines resulted in 15 randomized placebo-controlled trials (3734 patients), evaluating progesterone, erythropoietin and cyclosporine. The meta-analysis (15 studies) showed that TBI patients receiving a drug with anti-inflammatory effects had a higher chance of a favorable outcome compared to those receiving placebo (RR = 1.15; 95% CI 1.01–1.32, p = 0.041). However, publication bias was indicated together with heterogeneity (I2 = 76.59%). Stratified analysis showed that positive effects were mainly observed in patients receiving this treatment within 8 h after injury. Subanalyses by drug type showed efficacy for progesterone (8 studies, RR 1.22; 95% CI 1.01–1.47, p = 0.040), again heterogeneity was high (I2 = 62.92%) and publication bias could not be ruled out. The positive effect of progesterone covaried with younger age and was mainly observed when administered intramuscularly and not intravenously. Erythropoietin (4 studies, RR 1.20; p = 0.110; I2 = 76.59%) and cyclosporine (3 studies, RR 0.75; p = 0.189, I2 = 0%) did not show favorable significant effects. While negative findings for erythropoietin may reflect insufficient power, cyclosporine did not show better outcome at all. Current results do not allow firm conclusions on the efficacy of drugs with anti-inflammatory properties in TBI patients. Included trials showed heterogeneity in methodological and sample parameters. At present, only progesterone showed positive results and early administration via intramuscular administration may be most effective, especially in young people. The anti-inflammatory component of progesterone is relatively weak and other mechanisms than mitigating overall immune response may be more important.
“…Forty‐eight patients with axonal injury randomly received progesterone treatment within 4 hr of injury. Here, the progesterone group showed significantly better results than the control group (Soltani et al, ). In this context, it is believed that progesterone modulates the level of cytokines and reduces oxidant activity (Mofid et al, ).…”
The sex hormone progesterone is mainly known as a key factor in establishing and maintaining pregnancy. In addition, progesterone has been shown to induce morphological changes in the central and peripheral nervous system by increasing dendrito-, spino-, and synaptogenesis in Purkinje cells (Wessel et al.: Cell Mol Life Sci (2014a) 1723-1740 and increasing axonal outgrowth in dorsal root ganglia (Olbrich et al.: Endocrinology (2013) 3784-3795). These effects mediated mainly by the classical progesterone receptors (PRs) A and B seem to be limited to young neurons. It may be assumed that microRNAs (miRNAs), which are potent regulators of nervous system maturation and degeneration, are also involved in the regulation of progesterone-mediated neuronal plasticity by altering the expression patterns of the corresponding PR A/B receptors (Theis and Theiss: Neural Regen Res (2015) 547-549, Pieczora et al.: Cerebellum (2017) 376-387). This review critically discusses current data on the neuroprotective effect of progesterone and its corresponding receptors in the nervous system, with possible regulatory processes by miRNAs. Preclinical studies on stroke and traumatic brain injury revealed neuroprotective and neuroregenerative effects of progesterone in the treatment of severe neurological diseases in animal models, but have so far failed in humans. In this context, the identification of specific miRNAs that regulate the expression of progesterone and PR could help to exploit the neuroprotective potential of progesterone for the treatment of various neurological disorders. The human nervous system is a highly complex tissue composed of neurons and glial cells with a limited ability to regenerate after lesion or degeneration. In particular, the loss of neurons, for example, due to aging processes, stroke, or traumatic brain injury (TBI), is mostly irreversible. The function of the degenerating neurons can be partially compensated by neighboring neurons, but astroglial-fibrotic scar formation minimizes neuronal regeneration .Progesterone, a sexual hormone, is mainly known for its key role in the female reproductive circuit and the maintenance of pregnancy. In this context, the fact that progesterone is also expressed in the male organism is often neglected (Schumacher et al., 2014). Besides this, Abbreviations: BBB = blood brain barrier; CNS = central nervous system; DRG = dorsal root ganglia; GABA = Gamma-amino butyric acid; miRNA = microRNA; NMDAR = N-Methyl-D-aspartate receptor; PC = Purkinje cells; PGRMC1 = progesterone receptor membrane component 1; PNS = peripheral nervous system; PR = progesterone receptor; SCI = spinal cord injury; TBI = traumatic brain injury
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