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Thread: Antibiotic provides promise in treatment of spinal cord injuries

  1. #1
    Senior Member Jeremy's Avatar
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    Antibiotic provides promise in treatment of spinal cord injuries

    Antibiotic provides promise in treatment of spinal cord injuries

    Treatment prevents later-stage tissue loss contributing to long-term injury

    Researchers at Brigham and Women's Hospital (BWH) and Children's Hospital Boston (CHB) have found that a commonly prescribed antibiotic could be used to help prevent paralysis and other long-term functional deficits associated with a partial spinal cord injury (SCI). Researchers in the field have known that a significant proportion of paralysis and long-term functional disorders associated with SCI are triggered by post-trauma tissue loss. Administering the antibiotic, minocycline, to rats within the first hour after a paralyzing injury has been shown to reduce this tissue loss and ultimately enable more hind-leg function

    http://www.scienceblog.com/community/article2360.html

  2. #2
    Thanks Jeremy,

    The steroid methylprednisolone is currently used for SCI in clinical practice, but is falling into disfavor because of severe side effects.
    Hmm, not sure how accurate that statement is.

    Minocycline, a well-known neuroprotector that is currently being tested to treat stroke, ALS, Huntington's disease and head trauma, has no observable side effects in the rat model and can be given for up to an hour after SCI, providing a more realistic timeframe for clinical use.
    Since MP can be administered up to 8 hours after an injury it actually allows more flexibility than minocycline.

    "We believe that if minocycline is demonstrated effective in clinical trials of SCI, it will likely be part of a comprehensive cocktail of medications targeting the acute and chronic injuries of this devastating disease," said Robert M. Friedlander, MD of BWH, HMS associate professor of Neurosurgery and co-lead author of the study. "Because minocycline has already been proven as an effective neuroprotector and is capable of penetrating the blood-brain barrier, we believe that it may become the next-generation therapy for treating SCI."
    This is good news, especially if it shows promise for chronic injuries.

  3. #3
    jeremy, it is important to understand that several major clinical trials have shown that methylprednisolone improves neurological recovery when given early after spinal cord injury. The data supporting minocycline effects on spinal cord injury (particularly at the lower doses that are used for antibiotic purposes) is not yet convincing even in animal studies. There have been no clinical data at all concerning minocycline effects on neurological recovery. Finally, all these therapies refer to *acute* spinal cord injury and not chronic spinal cord injury.

    Wise.

  4. #4
    The words "comprehensive cocktail" that makes sense to me.

    Let's face it MP does have some side-effects..but can an antibiotic control
    the severe inflammation of an injured spinal
    cord? I don't know..but think not.

    But if the minocycline in reality does have
    certain neuroprotective qualities..can it
    enhance the protective qualities of MP?

    The article is so simply written with very
    little scientific facts to offer.
    If the injury is very minor we have found in
    dogs..sometimes complete rest can stop the
    negative processes.

    How did they injure the rats?
    Where they initially showing neurological
    losses before they were tested for gains?

    Maybe we can talk some of our more dedicated
    vets into trying this antibiotic when we are
    initially using the IV MP..see what happens.

    Most of our vets that use IV MP..will say
    if they see after the IV a 50% overall improvement in neurological functions..then we go the conservative treatment
    avenue..if less then that..myelogram or MRI
    and surgical consult.

    Thankfully some do see this 50%. Thank you
    Dr. Young..but many don't quite get there.
    If an antibiotic could help that would be great.

    <"();::::::::::;~

  5. #5
    Here are some of the abstracts of studies that have reported beneficial effects of high-dose minocycline in spinal cord injury:

    • Lee SM, Yune TY, Kim SJ, Park do W, Lee YK, Kim YC, Oh YJ, Markelonis GJ and Oh TH (2003). Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 20: 1017-27. Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea. We examined the effects of minocycline, an anti-inflammatory drug, on functional recovery following spinal cord injury (SCI). Rats received a mild, weight-drop contusion injury to the spinal cord and were treated with the vehicle or minocycline at a dose of 90 mg/kg immediately after SCI and then twice at a dose of 45 mg/kg every 12 h. Injecting minocycline after SCI improved hind limb motor function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. Twenty four to 38 days after SCI, BBB scores were significantly higher in minocycline-treated rats as compared with those in vehicle-treated rats. Morphological analysis showed that lesion size increased progressively in both vehicle-treated and minocycline-treated spinal cords. However, in response to treatment with minocycline, the lesion size was significantly reduced at 21-38 days after SCI when compared to the vehicle control. Minocycline treatment significantly reduced the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells 24 h after SCI as compared to that of the vehicle control. DNA gel electrophoresis also revealed a marked decrease in DNA laddering in response to treatment with minocycline. In addition, minocycline treatment significantly reduced the specific caspase-3 activity after SCI as compared to that of vehicle control. Furthermore, RT-PCR analyses revealed that minocycline treatment increased expression of interleukin-10 mRNA but decreased tumor necrosis factor-alpha expression. These data suggest that, after SCI, minocycline treatment modulated expression of cytokines, attenuated cell death and the size of lesions, and improved functional recovery in the injured rat. This approach may provide a therapeutic intervention enabling us to reduce cell death and improve functional recovery after SCI.
    See topic in SCI (Animal) Research Forum

    • Wells JE, Hurlbert RJ, Fehlings MG and Yong VW (2003). Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain. 126: 1628-37. University of Calgary, 3330 Hospital Drive, Calgary, Alberta, Canada T2N 4N1. vyong@ucalgary.ca. Acute spinal cord injury (SCI) produces tissue damage that continues to evolve days and weeks after the initial insult, with corresponding functional impairments. Reducing the extent of progressive tissue loss ('neuroprotection') following SCI should result in a better recovery from SCI, but treatment options have thus far been limited. In this study, we have tested the efficacy of minocycline in ameliorating damage following acute SCI in mice. This semi-synthetic tetracycline antibiotic has been reported to inhibit the expression and activity of several mediators of tissue injury, including inflammatory cytokines, free radicals and matrix metalloproteinases, making it a suitable candidate for study. Mice were subjected to extradural compression of the spinal cord using a modified aneurysm clip, following which they received treatment with either minocycline or vehicle beginning 1 h after injury. Behavioural testing of hindlimb function was initiated 3 days after injury using the Basso Beattie Bresnahan locomotor rating scale, and at 1 week using the inclined plane test. Functional assessments demonstrated that minocycline administration significantly improved both hindlimb function and strength from 3 to 28 days after injury compared with vehicle controls. Furthermore, gross lesion size in the spinal cord was significantly reduced by minocycline, and there was evidence of axonal sparing as determined using fluorogold labelling of the rubrospinal tract and by Bielchowsky silver stain. Finally, a comparison of minocycline against the currently approved treatment for acute SCI in humans, methylprednisolone, demonstrated superior behavioural recovery in the minocycline-treated animals.

    See topic in SCI (Animal) Research Forum

    Here are other stories reported previously in this forum for minocycline
    Acne drug may help spinal cord injuries...

    Brundula, et al. (2002). Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis.

    Minocycline - Any preliminary results

    Popovic, et al. (2002). Inhibition of autoimmune encephalomyelitis by a tetracycline.

    Wang, et al. (2002). Effects of minocycline alone and in combination with mild hypothermia in embolic stroke.

    PROJECT A.L.S.-Funded Researchers Detail How Common Acne Antibiotic Minocycline Delays Progression of Lou Gehrig's Disease

    Minocycline May Be Potential Treatment For MS

    Â*Detailed Analysis of Studies at the Society for Neuroscience Meeting Nov 11-15 San Diego

  6. #6
    Thanks Dr. Wise.
    I have previously read these write ups.
    I just have one question.

    All the studies use immediate application
    of high dose minocycline.

    We pretty much are assured that MP does it's
    job after the inflammatory process is advanced.

    It is almost an impossibility to get a human
    or animal to immediate care...
    Will the minocycline be as effective against
    the inflammatory process after say five hours
    as MP is?

    Would it be beneficial to use a combination
    of the two drugs?

    Thanks.

    <"();::::::::::;~

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