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    Study lithium

    very interesting article on lithium. wise young when you are going to publish the results of phase 1 of clinical trials on your lithium?

    GUERDENER







    http://www.scibx.com/scibx_main/20081009.html

    #2
    I read this paper,but couldn't make heads or tales of it. could somebody brake it down for me.. I know I'm not the sharpest knife in the kitchen LOL! But if someone could explain what that paper said and what it means I would be most grateful. thanks

    Comment


      #3
      my spin on it and i'm not that sharp either.

      The UT Southwestern researchers discovered that inhibiting glycogen synthase kinase 3beta (GSK3beta), an enzyme already implicated in neuronal polarity and axonal elongation,4, 5 induced neuron growth in cell culture and animal models of SCI.

      Cultured dorsal root ganglion neurons treated with either of two GSK3beta inhibitors—lithium or SB415286—had enhanced neurite outgrowth and axonal elongation in the presence of myelin and chondroitin sulfate proteoglycan (CSPG) compared with what was seen in cells that received vehicle control. Myelin and CSPG are known to inhibit neuronal growth in vivo following injury.

      Lithium is a generic noncompetitive inhibitor of GSK3beta that is marketed to treat mania associated with bipolar disorder. SB415286 is a small molecule competitive inhibitor of GSK3beta that was originally developed by SmithKline Beecham, now part of GlaxoSmithKline plc.6 The pharma company did not return calls regarding the status of SB415286.

      ---------------------

      they found that lithium helps stop some of the bad things that stop recovery after injury, thus allowing some recovery to happen.

      below that the other companies/groups also see promise in lithium.
      http://justadollarplease.org/

      2010 SCINet Clinical Trial Support Squad Member

      "You kids and your cures, why back when I was injured they gave us a wheelchair and that's the way it was and we liked it!" Grumpy Old Man

      .."i used to be able to goof around so much because i knew Superman had my back. now all i've got is his example -- and that's gonna have to be enough."

      Comment


        #4
        I took 300 mg of lithium a day for about two years after my accident. maybe three. I quit taking it when my liver counts rose. hurted my tummy.

        Comment


          #5
          Originally posted by jody View Post
          I took 300 mg of lithium a day for about two years after my accident. maybe three. I quit taking it when my liver counts rose. hurted my tummy.
          were you on it before your accident


          i wonder if someone was and their recovery was better than most at a certain level
          http://justadollarplease.org/

          2010 SCINet Clinical Trial Support Squad Member

          "You kids and your cures, why back when I was injured they gave us a wheelchair and that's the way it was and we liked it!" Grumpy Old Man

          .."i used to be able to goof around so much because i knew Superman had my back. now all i've got is his example -- and that's gonna have to be enough."

          Comment


            #6
            Originally posted by Leo View Post
            my spin on it and i'm not that sharp either.

            The UT Southwestern researchers discovered that inhibiting glycogen synthase kinase 3beta (GSK3beta), an enzyme already implicated in neuronal polarity and axonal elongation,4, 5 induced neuron growth in cell culture and animal models of SCI.

            Cultured dorsal root ganglion neurons treated with either of two GSK3beta inhibitors—lithium or SB415286—had enhanced neurite outgrowth and axonal elongation in the presence of myelin and chondroitin sulfate proteoglycan (CSPG) compared with what was seen in cells that received vehicle control. Myelin and CSPG are known to inhibit neuronal growth in vivo following injury.

            Lithium is a generic noncompetitive inhibitor of GSK3beta that is marketed to treat mania associated with bipolar disorder. SB415286 is a small molecule competitive inhibitor of GSK3beta that was originally developed by SmithKline Beecham, now part of GlaxoSmithKline plc.6 The pharma company did not return calls regarding the status of SB415286.

            ---------------------

            they found that lithium helps stop some of the bad things that stop recovery after injury, thus allowing some recovery to happen.

            below that the other companies/groups also see promise in lithium.
            Thanks Leo, still not crystal clear,but i think I understand the jist of it now! thanks again

            Comment


              #7
              kickingber,

              I'm pretty certain that the paper here is the same as the following poster presented at SfN:

              Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the cns (John Dill)
              Axonal regeneration is minimal after the CNS injuries in adult mammals and the medical treatments to recover the neurological loss due to axon disconnection are extremely limited. The nonpermissive environment and reduced intrinsic growth capacity are principally attributed to the failure for axonal elongation. In this report, we studied the role of glycogen synthase kinase-3 (GSK-3) inactivation on neurite and axon growth of adult neurons via combined in vitro and in vivo approaches. We found that the major CNS inhibiting substrates including chondroitin sulfate proteoglycans (CSPG) could inactivate protein kinase B (Akt) and activate GSK-3β signals in neurons. GSK-3 inactivation with pharmacologic inhibitors enhances neurite outgrowth of dorsal root ganglion neurons derived from adult mice or cerebellar granule neurons from postnatal rodents cultured on CNS inhibitors. Application of GSK-3 inhibitors stimulates axon formation and elongation of mature neurons whether in presence or absence of inhibitory substrates. Systemic application of GSK-3 inhibitor lithium to spinal cord-lesioned rats suppresses the activity of this kinase around lesion. Treatments with GSK-3 inhibitors including a clinical dose of lithium to rats with thoracic spinal cord transection or contusion injuries induce significant descending corticospinal and serotonergic axon sprouting in caudal spinal cord and promote locomotor functional recovery. Our studies suggest that GSK-3 signal is an important therapeutic target for promoting functional recovery of adult CNS injuries and that administration of GSK-3 inhibitors may facilitate the development of an effective treatment to white matter injuries including spinal cord trauma given the wide use of lithium in humans.
              • Funded by:
              • Paralyzed Veterans of America
              ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

              Comment


                #8
                I dont know if this helps but lithium is also known to stimulate proliferation of endogenous stem cells in the dendate gyrus (see abstract below)....now this is interesting since it appears to me that lithium has a variety of "regenerative" effects...it will be neat to see if other antidepressants that have been reported to stimulate endogenous stem cell proliferation may have funciton in spinal cord injury

                Neuropsychopharmacology. 2008 Nov 12. [Epub ahead of print] Links

                Glucocorticoids and Lithium Reciprocally Regulate the Proliferation of Adult Dentate Gyrus-Derived Neural Precursor Cells Through GSK-3beta and beta-Catenin/TCF Pathway.

                Boku S, Nakagawa S, Masuda T, Nishikawa H, Kato A, Kitaichi Y, Inoue T, Koyama T.
                1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
                Adult hippocampal neurogenesis is decreased in rodent models for stress-related disorders at least partly through an elevated level of glucocorticoids. On the other hand, the mood stabilizer lithium (Li) commonly used for their treatment increases it. This effect is thought to be one of the therapeutic actions of Li, but the molecular mechanism has been poorly understood. Here we established the culture system of adult rat dentate gyrus-derived neural precursor cells (ADPs) and examined the effects of dexamethasone (DEX), an agonist of glucocorticoids receptor, and Li on ADP proliferation. It is possible for ADP to be a type 2a cell, which corresponds to the second stage in a model of four differentiation stages in adult hippocampal neural precursor cells. DEX decreased ADP proliferation, but Li did not have any effect on it. However, Li recovered ADP proliferation decreased by DEX. The recovery effect of Li was abolished by quercetin, an inhibitor of beta-catenin/TCF pathway. The intranuclear translocation of beta-catenin and expression of cyclin D1 are reciprocally regulated by DEX and Li in a way similar to proliferation. In addition, DEX increased the phosphorylation of Tyr(216), which renders glycogen synthase kinase-3beta (GSK-3beta) active on it. These results suggest that GSK-3beta and beta-catenin/TCF pathway might be important in the reciprocal effects between DEX and Li on ADP proliferation and are new targets of therapeutic agents for stress-related disorders.Neuropsychopharmacology advance online publication, 12 November 2008; doi:10.1038/npp.2008.198.

                Comment


                  #9
                  oh crap i shouldnt have used that word "stem cell", it may remind you of Neil Riordan, and then you may get "offended", i apologize, lets just call it "progenitor cells" ok?

                  Comment


                    #10
                    lithium

                    \
                    Dear Guerdener

                    Can you be so kind to tell me how long after the spinal cord injury lithium administration takes place? Any info you have on this would be greatly appreciated. I checked www.clinicaltrials.gov and couldnt find it..thanks for your help

                    I ask becuase for stem cell administration post cardiac infarct it is published that if you dont administer within the first 7 days, therapeutic effect appears to be diminished

                    Christine






                    http://www.scibx.com/scibx_main/20081009.html[/quote]







                    http://www.scibx.com/scibx_main/20081009.html[/quote]

                    Comment


                      #11
                      Lithium to enhance autologous bone marrow

                      one of the problems i have with this field of regenerative medicine is that fiew studies are aiming to enhance clinically used approaches...people are already doing trials iwth lithium and also with autologous bone marrow cells for spinal cord injury...at least at face value it woudl be interesting to look at the two abstracts below

                      Exp Neurol. 2007 Aug;206(2):296-307. Epub 2007 Jun 2. Links

                      Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord.

                      Su H, Chu TH, Wu W.
                      Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
                      Transplantation of neural progenitor cells (NPCs) holds great potential for the treatment of spinal cord injuries. The survival and differential fates of transplanted NPCs in the cord are key factors contributing to the success of the therapy. In this study, we investigate the effects of lithium, a widely used antidepressant drug, on the survival, proliferation and differentiation of spinal cord-derived NPCs in cultures and after transplantation into the spinal cord. Our results show that clinically relevant doses of lithium increase the proliferation of grafted NPCs at 2 weeks post-grafting and neuronal generation by grafted NPCs at 2 weeks and 4 weeks post-grafting. However, lithium does not cause preferential differentiation of NPCs into astrocytes or oligodendrocytes both in vitro and after transplantation. Our results also show that chronic treatment with lithium (up to 4 weeks) reduces microglia and macrophage activation, indicating that lithium treatment can affect the host immune response. The results of the present study provide evidence that lithium may have therapeutic potential in cell replacement strategies for CNS injury due to its ability to promote proliferation and neuronal generation of grafted NPCs and reduce the host immune reaction.


                      Stem Cells. 2007 Aug;25(8):2066-73. Epub 2007 Apr 26. Links

                      Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial.

                      Yoon SH, Shim YS, Park YH, Chung JK, Nam JH, Kim MO, Park HC, Park SR, Min BH, Kim EY, Choi BH, Park H, Ha Y.
                      Inha Neural Repair Center, Department of Neurosurgery, Inha University College of Medicine, 7-206, Sinheung-dong 3-ga, Jung-Gu, Incheon, Korea.
                      To assess the safety and therapeutic efficacy of autologous human bone marrow cell (BMC) transplantation and the administration of granulocyte macrophage-colony stimulating factor (GM-CSF), a phase I/II open-label and nonrandomized study was conducted on 35 complete spinal cord injury patients. The BMCs were transplanted by injection into the surrounding area of the spinal cord injury site within 14 injury days (n = 17), between 14 days and 8 weeks (n = 6), and at more than 8 weeks (n = 12) after injury. In the control group, all patients (n = 13) were treated only with conventional decompression and fusion surgery without BMC transplantation. The patients underwent preoperative and follow-up neurological assessment using the American Spinal Injury Association Impairment Scale (AIS), electrophysiological monitoring, and magnetic resonance imaging (MRI). The mean follow-up period was 10.4 months after injury. At 4 months, the MRI analysis showed the enlargement of spinal cords and the small enhancement of the cell implantation sites, which were not any adverse lesions such as malignant transformation, hemorrhage, new cysts, or infections. Furthermore, the BMC transplantation and GM-CSF administration were not associated with any serious adverse clinical events increasing morbidities. The AIS grade increased in 30.4% of the acute and subacute treated patients (AIS A to B or C), whereas no significant improvement was observed in the chronic treatment group. Increasing neuropathic pain during the treatment and tumor formation at the site of transplantation are still remaining to be investigated. Long-term and large scale multicenter clinical study is required to determine its precise therapeutic effect. Disclosure of potential conflicts of interest is found at the end of this article.

                      Comment


                        #12
                        An article about lithium to this community is on my list of articles to write. By the way, I am writing an article a day, trying to limit each article to 1000 words. Unfortunately, the last three articles that I have written have each been 10,000 words and have taken me more time than I had planned.

                        I just posted on http://wiseyoung.wordpress.com/ an article that details the answer to the first frequently asked question "Will There Be A Cure for Spinal Cord Injury". I am currently writing "When Will There Be A Cure for Spinal Cord Injury". Once I am through with that, I will go back and expand on each of the significant areas, including lithium.

                        I am hoping to write an article a day with the goal of contributing 1000 articles to a Spinal Cord Injury Wiki that people can then add, modify, and extend.

                        Wise.

                        Comment


                          #13
                          http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

                          Comment


                            #14
                            Here I've collected excerpts on Lithium from numerous sources:
                            "Let your food be your medicine" - Hippocrates

                            Comment


                              #15
                              still not published the Phase 1 of lithium in humans?

                              thank you

                              guerdener

                              Comment

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