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Thread: Lipoic acid for SCI treatment

  1. #1

    Lipoic acid for SCI treatment

    Lipoic acid might be useful for those with neuropathic pain and maybe as part of a combinatorial strategy for treatment of spinal cord injury.

    From 2009:
    5. Clinical and therapeutic effects of LA
    5.1. Diabetic polyneuropathies
    The interaction of LA with regulatory components of the insulin- signaling cascade has proved functionally beneficial to skeletal muscle glucose uptake, whole-body glucose tolerance, and helpful against insulin resistance in animal models [118,120]. Improvements in glucose disposal were also observed in human patients with type 2 diabetes receiving LA either intravenously or orally [120122]. Several clinical trials have been conducted to measure the efficacy of racemic LA in decreasing symptoms of diabetic polyneuropathies; these are the alpha-lipoic acid in diabetic neuropathy(ALADIN) trials and the symptoms of diabetic polyneuropathy(SYDNEY) trials. LA was given orally, intravenously, or i.v. with oral follow-up. A meta-analysis of four clinical trials using i.v. LA, including ALADIN, SYDNEY, and the first 3 weeks of ALADIN III, showed a significant improvement in diabetic polyneuropathies of the feet and lower limbs in patients infused with LA 600 mg/day, for three weeks [123]. Diabetic patients in the ALADIN II trial were administered with LA i.v. at 600 or 1200 mg/day for 5 days, then oral LA for 2 years, resulting in improved indices of neuropathy [38]. Patients in the ALADIN III study received LA (600 mg/day i.v.) or placebo for three weeks, followed by oral LA (600 mg t.i.d.) or placebo for 6 months. The oral phase of this trial, however, was without clinically significant benefits [39]. One possible conclusion from these studies was that LA administered intravenously was more efficacious than oral LA, which may be due to either greater bioavailability or poor solubility of the medication in the stomach acid. However, some additional studies have found that oral LA is very effective. For example, the oral pilot (ORPIL) study showed a reduction in diabetic polyneuropathic symptoms after three weeks with 600 mg LA t.i.d. [41]. While the first SYDNEY trial used i.v. LA, [42], the SYDNEY II study used oral LA at 600, 1200, or 1800 mg q.d. for 5 weeks [43]; consequently, both studies showed significant improvements in neuropathic endpoints.
    There is evidence lipoic acid acts similarly to lithium on neurite outgrowth.
    From 2011:
    1. Int J Dev Neurosci. 2011 Jun;29(4):415-22. doi: 10.1016/j.ijdevneu.2011.03.001. Epub 2011 Mar 21. MEK/ERKs signaling is essential for lithium-induced neurite outgrowth in N2a cells. Wang Z, Wang J, Li J, Wang X, Yao Y, Zhang X, Li C, Cheng Y, Ding G, Liu L, Ding Z. Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, China. Lithium, a drug used for the treatment of bipolar disorder, has been shown to affect different aspects of neuronal development such as neuritogenesis, neurogenesis and survival. The underlying mechanism responsible for lithium's influence on neuronal development, however, still remains to be elucidated. In the present study, we demonstrate that lithium increases the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt) and promotes neurite outgrowth in mouse N2a neuroblastoma cells (N2a). The inactivation of mitogen-activated protein kinase kinase (MEK)/ERKs signaling with a MEK inhibitor inhibits neurite outgrowth, but it enhances Akt activation in lithium-treated N2a cells. Furthermore, the inactivation of phosphoinositide-3-kinase (PI3K)/Akt signaling with a PI3K inhibitor increases both lithium-induced ERKs activation and lithium-induced neurite outgrowth. Taken together, our study suggests that lithium-induced neurite outgrowth in N2a cells is regulated by cross-talk between the MEK/ERKs and PI3K/Akt pathways and requires the activation of the MEK/ERKs signaling.
    1. Biochim Biophys Acta. 2011 May;1813(5):827-38. doi: 10.1016/j.bbamcr.2011.01.027. Epub 2011 Feb 2. Essential role of ERK activation in neurite outgrowth induced by α-lipoic acid. Wang X, Wang Z, Yao Y, Li J, Zhang X, Li C, Cheng Y, Ding G, Liu L, Ding Z. Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. BACKGROUND: Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth. METHODS: To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth. RESULTS: LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth. CONCLUSION: Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

  2. #2
    Senior Member ian's Avatar
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    I would like to see trials of ALA in acute spinal cord injury, 7 years ago when my daughter was injured I attempted to persuade her Doctors to allow me to or for them to administer this to her. They refused to even look at the literature.

  3. #3
    Quote Originally Posted by ian View Post
    I would like to see trials of ALA in acute spinal cord injury, 7 years ago when my daughter was injured I attempted to persuade her Doctors to allow me to or for them to administer this to her. They refused to even look at the literature.
    Here are a couple that were done in animals.
    1. J Spinal Cord Med. 2010;33(4):401-9. Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats. Toklu HZ, Hakan T, Celik H, Biber N, Erzik C, Ogunc AV, Akakin D, Cikler E, Cetinel S, Ersahin M, Sener G. Marmara University School of Pharmacy, Department of Pharmacology, Istanbul, Turkey. haletoklu@yahoo.com BACKGROUND: Oxidative stress is a mediator of secondary injury to the spinal cord following trauma. OBJECTIVE: To investigate the putative neuroprotective effect of alpha-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI). METHODS: Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. RESULTS: SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged. CONCLUSION: The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.
    1. Acta Neurochir (Wien). 2010 Sep;152(9):1591-600; discussion 1600-1. doi: 10.1007/s00701-010-0703-9. Epub 2010 Jun 10. Anti-apoptotic and neuroprotective effects of α-lipoic acid on spinal cord ischemia-reperfusion injury in rabbits. Emmez H, Yildirim Z, Kale A, Tönge M, Durdağ E, Börcek AO, Uçankuş LN, Doğulu F, Kiliç N, Baykaner MK. Department of Neurosurgery, Faculty of Medicine, Gazi University, Polikliniği Kat 1, Ankara 06500, Turkey. alpborcek@gmail.com PURPOSE: Radical oxygen species produced after injury counteracts antioxidant activity and frequently causes severe oxidative stress for the tissues. Alpha-lipoic acid is a powerful metabolic antioxidant with immunomodulatory effects which provides neuroprotection. The aim of this study is to investigate the neuroprotective and anti-apoptotic effects of alpha-lipoic acid on spinal cord ischemia-reperfusion. METHODS: Twenty-four adult, male, New Zealand rabbits were divided into sham (n = 8), control (n = 8), and treatment groups (n = 8). The abdominal aorta was clamped for 30 min by an aneurysm clip, approximately 1 cm below the renal artery and 1 cm above the iliac bifurcation in control and treatment groups. Only laparotomy was performed in the sham group. Twenty-five cubic centimeters of saline in control group and 100 mg/kg lipoic acid were administered intraperitoneally in the treatment group after closure of the incision. The animals were killed 48 h later. Spinal cord segments between L2 and S1 were harvested for analysis. Levels of nitric oxide, glutathione, malondialdehyde, advanced oxidation protein products, and superoxide dismutase were analyzed as markers of oxidative stress and inflammation. Caspase-3 activity was analyzed to detect the effect of lipoic acid on apoptosis. RESULTS: In all measured parameters of oxidative stress, administration of lipoic acid significantly demonstrated favorable effects. Both plasma and tissue levels of nitric oxide, glutathione, malondialdehyde, and advanced oxidation protein products significantly changed in favor of antioxidant activity. There was no significant difference between the plasma superoxide dismutase levels of the groups. Histopathological evaluation of the tissues also demonstrated significant decrease in cellular degeneration and infiltration parameters after lipoic acid administration. However, lipoic acid has no effect on caspase-3 activity. CONCLUSIONS: Although further studies considering different dose regimens and time intervals are required, the results of the present study prove that alpha-lipoic acid has favorable effects on experimental spinal cord ischemia-reperfusion injury.

  4. #4
    Senior Member ian's Avatar
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    This is the sort of thing they can be trying now on acute sci injuries in my opinion, there is no need for trials to test for safety. This is a supplement freely available, unpatented and which has already been used on humans for other purposes for decades. I would combine it with this http://en.wikipedia.org/wiki/Curcumin

  5. #5
    Senior Member Van Quad's Avatar
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    Quote Originally Posted by ian View Post
    This is the sort of thing they can be trying now on acute sci injuries in my opinion, there is no need for trials to test for safety. This is a supplement freely available, unpatented and which has already been used on humans for other purposes for decades. I would combine it with this http://en.wikipedia.org/wiki/Curcumin
    Good suggestion. I would also include fish oil. And acupuncture.

  6. #6
    I have been using Alpha Lipoic Acid myself since it was recommended to me by my physiatrist and can easily be obtained from a supplement supplier which sells, vitamins, etc. and I have obtained recovery of sensation below the level of injury.

  7. #7
    Quote Originally Posted by Ryan B View Post
    I have been using Alpha Lipoic Acid myself since it was recommended to me by my physiatrist and can easily be obtained from a supplement supplier which sells, vitamins, etc. and I have obtained recovery of sensation below the level of injury.
    Ok this is the 3rd post ive read by you, where you have said to have gained recovery because of something... So let me ask you this: was is the nicotine, Hydrogen Peroxide, Lipoic acid, or Proteolytic Enzymes that help you get some return after spinal cord injury?
    Last edited by Barrington314mx; 03-25-2013 at 07:55 PM.

  8. #8


    Neuralyn man! thats where tha cure is........................

    Newbies, they're always finding cures in potions, vitamins, massage therapists and of course intravenous injections of anything called a stem cell.
    "I'm manic as hell-
    But I'm goin' strong-
    Left my meds on the sink again-
    My head will be racing by lunchtime"

    <----Scott Weiland---->

  9. #9
    Senior Member ian's Avatar
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    Quote Originally Posted by ineedmyelin View Post


    Neuralyn man! thats where tha cure is........................

    Newbies, they're always finding cures in potions, vitamins, massage therapists and of course intravenous injections of anything called a stem cell.
    I dont think it serves us too well to ridicule posts like this. No one has mentioned these things in this thread and ALA is not a vitamin or a potion. Given what is now known about acute sci injuries it is obvious that preventing inflammation may be the key to enhanced recovery.

  10. #10
    Quote Originally Posted by ian View Post
    I dont think it serves us too well to ridicule posts like this. No one has mentioned these things in this thread and ALA is not a vitamin or a potion. Given what is now known about acute sci injuries it is obvious that preventing inflammation may be the key to enhanced recovery.
    And it sure as hell doesnt serve anyone ESPECIALLY a newly injured person to
    to suggest that by loading up on Alpha Lipoic Acid, nicotine, Hydrogen Peroxide, Lipoic acid, or Proteolytic Enzymes will regenerate injured/damaged spinal cord.
    "I'm manic as hell-
    But I'm goin' strong-
    Left my meds on the sink again-
    My head will be racing by lunchtime"

    <----Scott Weiland---->

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