Hi There, I suffered a rather severe herniation of the C6 vertebrae in my neck which resulted in about 60% loss of strength in my left arm & muscle atrophy in my upper back/deltoid area as well. I had pretty extensive damage, and it has taken about 20 months to heal. I am now at 95% or better. During the course of this time I tried many self administered treatments, as I was told by the spine doc that surgery or simply making lifestyle changes were my only 2 options. Ultimately, its time that will allow the body to repair the disk and regrow damaged nerves. That being said, these are my experiences with my own treatments during that time:
1) B vitamins seemed to help slightly with speeding up recovery. I used a sub-lingual 5,000mcg B12 + Niacinimide + B6 4-5 times a week. There is research you can pull up regarding B's and nerve health
2) Anabolic Steroids - Do not try.. made it worse actually, DHT derivatives are bad news for the movable parts of the body (joints, discs etc). They have a drying effect on these areas. There's a good bit of reearch on this as well.
3) Growth Hormone Peptides (100mcg sermorelin + 100mcg Ipamorelin SubQ daily) - I noticed a considerable increase in the healing rate once I started this regimen. Its actually improved many aspects of my ageing body, most noticeably a marked decrease in chronic inflammation and joint aches etc.Its a treatment that you'll have to weight pros/cons yourself and decide.
4) Thymosin Beta 4 (also known as TB500) - Made the most dramatic difference for me. Before starting on this peptide I was about 75% healed, and within weeks of starting this I jumped to 95% and have remained there. I took 2mg (subQ) twice a week for 6 weeks. That was enough to pretty much finish the job
Again, make your own decisions on this sort of thing. Here's some research on this interesting compound that may help:
(Note: credit goes to Dat for the research - I provide it here in the hopes it helps someone else like it did me)
Thymosin Beta 4--------------------------------------------------Disc degeneration
Lumbar degenerative disease, which leads to lower back pain, is an endurance that aging man faces. Degenerative disc disease results from the loss by apoptosis of annulus cells, which make up the outer fibrous capsule of the intervertebral disk. A study conducted at three major medical institutions reported that Tβ4 significantly reduced disc cell apoptosis, suggesting a potential treatment for degenerative disc disease and chronic discogenic lower back pain.
That study was Exogenous thymosin beta4 prevents apoptosis in human intervertebral annulus cells in vitro, Tapp H, Biotech Histochem. 2009 Dec;84(6):287-94
Abstract
Loss of cells in the human disc due to programmed cell death (apoptosis) is a major factor in the aging and degenerating human intervertebral disc. Our objective here was to determine if thymosin beta(4) (TB4), a small, multifunctional 5 kDa protein with diverse activities, might block apoptosis in human annulus cells cultured in monolayer or three-dimensional (3D) culture.
Apoptosis was induced in vitro using hydrogen peroxide or serum starvation. Annulus cells were processed for identification of apoptotic cells using the TUNEL method. The percentage of apoptotic cells was determined by cell counts. Annulus cells also were treated with TB4 for determination of proliferation, and proteoglycan production was assessed using cell titer and 1,2 dimethylmethylamine (DMB) assays and histological staining.
A significant reduction in disc cell apoptosis occurred after TB4 treatment. The percentage of cells undergoing apoptosis decreased significantly in TB4 treated cells in both apoptosis induction designs. TB4 exposure did not alter proteoglycan production as assessed by either DMB measurement or histological staining. Our results indicate the need for further studies of the anti-apoptotic effect of TB4 and suggest that TB4 may have therapeutic application in future biological ----------------------------------------------------Thymosin β4 promotes the recovery of peripheral neuropathy in type II diabetic mice, Lei Wang, Neurobiology of Disease Volume 48, Issue 3, December 2012, Pages 546–555
Abstract
Peripheral neuropathy is one of the most common complications of diabetes mellitus. Using a mouse model of diabetic peripheral neuropathy, we tested the hypothesis that thymosin β4 (Tβ4) ameliorates diabetes‐induced neurovascular dysfunction in the sciatic nerve and promotes recovery of neurological function from diabetic peripheral neuropathy. Tβ4 treatment of diabetic mice increased functional vascular density and regional blood flow in the sciatic nerve, and improved nerve function. Tβ4 upregulated angiopoietin-1 (Ang1) expression, but suppressed Ang2 expression in endothelial and Schwann cells in the diabetic sciatic nerve. In vitro, incubation of Human Umbilical Vein Endothelial Cells (HUVECs) with Tβ4 under high glucose condition completely abolished high glucose-downregulated Ang1 expression and high glucose-reduced capillary-like tube formation. Moreover, incubation of HUVECs under high glucose with conditioned medium collected from Human Schwann Cells (HSCs) treated with Tβ4 significantly reversed high glucose-decreased capillary-like tube formation. PI3K/Akt signaling pathway is involved in Tβ4-regulated Ang1 expression on endothelial and Schwann cells. These data indicate that Tβ4 likely acts on endothelial cells and Schwann cells to preserve and/or restore vascular function in the sciatic nerve which facilitates improvement of peripheral nerve function under diabetic neuropathy. Thus, Tβ4 has potential for the treatment of diabetic peripheral neuropathy.
Introduction
Peripheral neuropathy is one of the most common and disabling complications of diabetes mellitus. Studies of diabetic peripheral neuropathy from experimental animals and humans indicate that the development of diabetic neuropathy is closely associated with marked neurovascular dysfunction (Cameron et al., 2001; Ebenezer et al., 2011; Tesfaye et al., 1993). Vascular dysfunction precedes the appearance of nerve conduction velocity deficits, leading to nerve damage (Cameron and Cotter, 1999; Cameron et al., 2005; Ebenezer et al., 2011). Therapies targeting neurovascular function have been shown to restore nerve function in experimental diabetic peripheral neuropathy (Ii et al., 2005; Kusano et al., 2004; Schratzberger et al., 2001).
Thymosin Beta4 (Tß4), a small 4.9 kDa polypeptide of 43 amino acids, is a major intracellular G-actin-sequestering peptide (Goldstein et al., 1996) and is present in almost all cell types (Crockford et al., 2010). Tß4 has multiple biological functions that include promoting diabetic wound healing by repairing and regenerating damaged tissues (Philp et al., 2003) and enhancing angiogenesis after myocardial infarction and vasculogenesis during development (Crockford, 2007; Smart et al., 2007a). Tß4 is currently under a phase II clinical trial for the treatment of patients with acute myocardial infarction (ClinicalTrials.gov,http://clinicaltrial...ow/NCT01311518; Ruff et al., 2010). In the central nervous system, preclinical studies show that Tß4 has neuroprotective and neurorestorative effects by reducing neuronal damage and enhancing oligodendrogenesis, which lead to improvement of neurological outcomes after stroke, traumatic brain injury and multiple sclerosis (Morris et al., 2010; Philp et al., 2003; Xiong et al., 2011; Zhang et al., 2009). However, the effect of Tß4 on peripheral nerves, such as diabetic peripheral neuropathy, has not been invetigated.
The angiopoietins (Ang1 and Ang2) and their receptor Tie-2 regulate vascular development and homeostasis (Suri et al., 1996; Teichert-Kuliszewska et al., 2001). Ang-1 promotes vascular stabilization and maturation whereas Ang2 acts as a partial agonist or antagonist of Ang1 signaling, depending on vascular endothelial growth factor (VEGF) bioavailability (Maisonpierre et al., 1997; Suri et al., 1996; Thebaud et al., 2005). The Ang/Tie2 signaling pathway plays an important role in mediating vascular function under diabetes (Chen and Stinnett, 2008b; Tuo et al., 2008). Hyperglycemia downregulates Ang1 and upregulates Ang2, which exacerbates myocardial infarction (Morris et al., 2010; Tuo et al 2008). Increases in Ang1 levels normalize diabetes induced immature vasculature (Chen and Stinnett, 2008a). Patients with peripheral diabetic neuropathy have elevated levels of circulating Ang2 (Rasul et al., 2011). However, the effect of the Ang/Tie2 signaling pathway on peripheral diabetic neuropathy has not been extensively studied.
In the present study, using a mouse model of type II diabetes, we tested the hypothesis that treatment of diabetic peripheral neuropathy with Tß4 ameliorates neurovascular dysfunction and improves peripheral nerve function. In addition, we investigated the effect of Tß4 on the Ang/Tie2 signaling pathway under conditions of diabetic peripheral neuropathy.
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Discussion
The present study for the first time demonstrates that Tß4 significantly improved sciatic nerve vascular function and peripheral nerve function in a mouse model of diabetic peripheral neuropathy. The Ang/Tie2 signaling pathway likely mediates the effect of Tß4 on improved vascular function.
Tß4, a naturally occurring peptide, enhances heart regeneration after myocardial infarction and promotes brain repair after stroke (Bock-Marquette et al., 2004; Morris et al., 2010). However, the effect of Tß4 on diabetic peripheral neuropathy has not been investigated. Using a well established mouse model of type II diabetes, the present study indicates that Tß4 ameliorates diabetic peripheral neuropathy, evidenced by reduction of sciatic nerve conduction velocity deficits, a key parameter for diabetic peripheral neuropathy, and improves responses to thermal stimuli. These data suggest that Tß4 has potential for the treatment of diabetic peripheral neuropathy.
Studies of diabetic peripheral neuropathy from experimental animals and human indicate that the development of diabetic neuropathy is closely associated with marked neurovascular dysfunction (Cameron et al., 2001; Ebenezer et al., 2011; Tesfaye et al., 1993). Vascular dysfunction precedes appearance of nerve conduction velocity de?cits, leading to nerve damage (Cameron and Cotter, 1999; Cameron et al., 2005; Ebenezer et al., 2011). Our data demonstrated that Tß4 substantially increased plasma-perfused vessels and regional blood flow in the sciatic nerve, concomitantly with improvement of neurological function of diabetic neuropathy, suggesting that normalization of vascular function by Tß4 may contribute to observed reduction of nerve conduction velocity deficits. Our findings are consistent with prior reports that restoration of vascular function by either pro-angiogenic factors or cell therapies enhances neurological function in diabetic peripheral neuropathy (Ii et al., 2005; Jeong et al., 2009; Kusano et al., 2004). However, further studies on the direct effects of Tß4 on nerve fiber morphology and its relationship to improvement in neurological function are warranted. Our data show that Tß4 at doses of 6 and 24 mg/kg significantly improved neurological outcome. Currently, we do not know why a dose of 24 mg/kg is not superior to a lower dose of 6 mg/kg to improve vascular function and neurological outcomes in diabetic mice with peripheral neuropathy. We previously demonstrated that Tß4 at a dose of 30 mg/kg significantly reduces brain injury and improves neurological outcome compared to a dose of 6 mg/kg (Xiong et al., 2012). A clinical phase 1A and 1B study demonstrates that Tß4 at a dose range of 42 to 1260 mg daily for 2 weeks did not have adverse effects, suggesting that Tß4 has a large dose range in human (RegeneRx Biopharmaceuticals Inc). Further studies on the effects of doses at 30 mg/kg and higher on diabetic peripheral neuropathy are warranted.
The Ang/Tie2 signaling pathway regulates vascular homeostasis (Suri et al., 1996; Teichert-Kuliszewska et al., 2001). Ang1 promotes vascular maturation, while Ang2 acts as a competitive inhibitor of Ang1 for Tie2 binding and destabilizes blood vessels (Maisonpierre et al., 1997; Suri et al., 1996; Thebaud et al., 2005). Hyperglycemia downregulates Ang1 and upregulates Ang2 (Tuo et al., 2008). Increases in Ang1 levels normalize diabetes induced immature vasculature (Chen and Stinnett, 2008a). Ang1 by increasing angiogenesis reduces myocardial infarction, whereas an elevation of Ang2 levels exacerbates the infarction in diabetic rats (Tuo et al., 2008). Patients with diabetic peripheral neuropathy have significantly elevated levels of circulating Ang2 (Rasul et al., 2011). Our data show that hyperglycemia downregulated Ang1 and upregulated Ang2 on endothelial cells and Schwann cells, whereas Tß4 reversed expression of Ang1 and Ang2. Tß4 is a potent angiogenic factor and regulates angiogenesis and vasculogenesis during development by promoting progenitor cell differentiation and by directing endothelial cell migration (Bock-Marquette et al., 2004; Smart et al., 2007a, b). The effect of Tß4 on the Ang/Tie2 pathway has not been investigated. Our data that blockage of Tie2 with a neutralizing antibody suppressed the effect of Tß4 on in vitro angiogenesis implicate the Ang/Tie2 signaling pathway in mediating Tß4-improved vascular function observed in vivo. Our data further suggest that Tß4 regulates Ang1 through the activation of the PI3K/Akt pathway. A recent study shows that Tß4 interacts with ATP-responsive P2X4 receptor to regulate endothelial cell migration (Freeman et al., 2011). Angiogenesis involves endothelial cell proliferation and migration (Goukassian et al., 2001; Wang et al., 2011b). Therefore, further studies are warranted for investigating whether purinergic signaling is involved in the bene?cial effects of Tß4 observed in the present study.
Schwann cells secrete numerous factors that regulate degeneration and regeneration peripheral nerves (Campana, 2007; Frostick et al., 1998; Sobue, 1990). The present study showed that Ang1 and Ang2 secreted by Schwann cells affected endothelial function under hyperglycemia condition, while Tß4-elevated Ang1 levels on Schwann cells lead to enhancement of in vitro angiogenesis. We speculate that Tß4 acts on endothelial cells and Schwann cells to preserve and/or restore vascular function in the sciatic nerve, which facilitates improvement of peripheral nerve function under diabetic neuropathy.----------------------------------------------------------------------------------Thymosin Beta 4 Induces Hair Growth via Stem Cell Migration and Differentiation, DEBORAH PHILP, Ann. N.Y. Acad. Sci. 1112: 95–103 (2007)
ABSTRACT:
Thymosin beta 4 is a small 43-amino-acid molecule that has multiple biological activities, including promotion of cell migration angiogenesis, cell survival, protease production, and wound healing. We have found that thymosin beta 4 promotes hair growth in various rat and mice models including a transgenic thymosin beta 4 overexpressing mouse. We have also determined the mechanism by which thymosin beta 4 acts to promote hair growth by examining its effects on follicle stem cell growth, migration, differentiation, and protease production.
THYMOSIN BETA 4 HAS MULTIPLE BIOLOGICAL ACTIVITIES
Thymosin beta 4 is a small, 43-amino-acid, actin-binding, intracellular protein that is present in all cells.1 It was originally identified in endothelial cells as a gene that was increased during early endothelial cell capillary formation.2 It was later shown to actually promote capillary formation in vitro and angiogenesis in vivo in a number of model systems.3,4 Since then, an unexpectedly large number of important biological activities of thymosin beta 4 have been identified (TABLE 1). Because it is high in platelets, its role in wound healing was investigated, and it was found to promote dermal healing in normal rats and mice as well as in impaired models of dermal wound healing, including aged mice, diabetic mice, and steroid-treated rats.5,6 Thymosin beta 4 was also shown to have an important role in corneal wound healing and in cardiac repair.7,8
TABLE 1. Biological activities of thymosin beta 4 - Increased migration: endothelial cells, epithelial cells, stem cells, keratinocytes
- Increased cell survival
- Increased differentiation, endothelial cells, stem cells
- Increased proteases: monocytes, fibroblasts, endothelial cells, stem cells, corneal cells
- Decreased (+)inflammation
- Increased angiogenesis: in vitro, ex vivo, in vivo
- Increased dermal healing: rats, mice, aged mice, diabetic mice, steroid-treated rats
- Increased corneal healing: rats, mice
- Increased hair growth
- Increased (-) but passive role only)) tumor growth
- Increased gene expression: laminin-5, zyxin, TFG beta, TIMPs (1–3)
Part of its role in healing may be due to its ability to reduce inflammation. 9 Surprisingly, it has been shown to induce proteases by a number of cell types, and this activity is important in cell migration and in wound repair. 10,11 We have also found that TIMPs, which are protease inhibitors, are also increased by thymosin beta 4 (TABLE 1).
Thymosin beta 4 has been found by a number of labs to promote tumor growth (-).12–14 This activity is due to its ability to promote cell migration and angiogenesis.12 It also increases vascular endothelial growth factor (VEGF) expression, which can promote cell migration and angiogenesis. It does not appear to be due to oncogenic activity, but rather has a passive role in promoting tumor growth. When animals are treated topically every day with thymosin beta 4, no tumors have been observed. Also, mice overexpressing high levels of this gene in their skin do not form an increased number of spontaneous tumors with age.
While we are beginning to understand a lot about the biological functions of thymosin beta 4 and its potential uses in the clinic, a number of unanswered questions remain on how it regulates it biological functions. We have begun to identify regions on the molecule important for some of the activities, such as the central actin-binding domain that promotes wound healing and angiogenesis.15 The amino terminal amino acids are important in regulating inflammation.16 Such progress has defined important activities, but a receptor has not been identified. Also, it is not clear how the signal is transduced in the cells.
Edited by PatrickM500, 12 July 2013 - 03:44 PM.
