DMSO question for Dr. Young
I copied this off the site Meeker posted about on the Omenentum Transportation. I was given DMSO after my SCI in 1981 at Boston University Medical Center and I still ended up a complete t-4 Para, I sometimes wonder if I had been given it earlier that maybe I would be walking. I believe I was started on it about 24 hours after my injury, heck I laid on my back in the ER for 4 hours while they questioned me with financial responsibility questions.
Anyhow, my question is, Do you feel that this combined with the drug Methalyprednasone could increase the chance of recovery if both adminstered within an hour of injury? Or is there not enough data to make any conclusions?.
DMSO Protects the Spine In The Acute Phase
ﾃつ*ﾃつ*ﾃつ*ﾃつ*First, let's talk about dimethyl sulfoxide (DMSO), a unique substance that prevents spinal cord damage, including paralysis, if administered within one hour of injury.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*DMSO works on three principles. ﾃつ*It is the most powerful known hydroxy radical scavenger. ﾃつ*Injury to the spinal cord generates a cascade of hydroxy free radicals that extend the damage by killing the cells of the spinal cord. ﾃつ*DMSO's unique anti-oxidant activity effectively interrupts this damaging chain of vents before neural tissues are destroyed.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*Second, DMSO is a powerful anti-inflammatory agent and dramatically reduces swelling. ﾃつ*this is of vital importance in spinal cord injuries, as it is compression of the nerves and tissues, as they swell inside the bony spinal column (or skull in a head injury) and cut off blood supply and oxygen delivery, which is thought to render most of the damage to the spinal cord or brain. ﾃつ*DMSO increases blood flow and oxygen to the injured area.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*Third, DMSO actually reduces the amount of oxygen needed by the cells. ﾃつ*No one knows how it does this, but there is no question that DMSO alters the oxygen dynamics of individual cells. ﾃつ*This is obviously important in any injury, as oxygen deprivation leads to cell death and permanent damage.
Animal Studies With DMSO Are Convincing
ﾃつ*ﾃつ*ﾃつ*ﾃつ*Extensive animal research has demonstrated that DMSO significantly reduces the effects of spinal cord or head trauma if administered shortly after injury. ﾃつ*In one particular dramatic study, 24 mongrel dogs were anesthetized and the blood supply to the midsection of the spinal cord was shut off. ﾃつ*Twelve of the dogs received a saline solution and the other 12 received a solution of DMSO. ﾃつ*The procedure lasted for 30 minutes.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*At the end of the experiment, 11 of the 12 control animals (receiving saline solution) had complete paralysis in the lower extremities, with only one having any perceptible movement in his joints. ﾃつ*However, in the DMSO group 11 of the 12 had complete recovery and could walk and run, with the remaining dog having only slight weakness. ﾃつ*There was also microscopic evidence ischemic changes and cell damage in the control group but not in those which received DMSO.
A Quadriplegic Walked Out Of The Hospital
After DMSO Treatment
ﾃつ*ﾃつ*ﾃつ*ﾃつ*There have been a few cases in which DMSO was successfully used to treat humans with spinal cord injuries. ﾃつ*J.C. De la Torre, M.D., one of the early DMSO researchers, documented a case 20 years ago that should have opened the door for intensive research.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*A patient was admitted to a hospital in Chicago with an "incomplete" spinal cord injury - he had function from the neck downward. ﾃつ*However, when he was being shifted to a bed in the hospital, his neck was moved, the injury was exacerbated, and the patient became completely quadriplegic, exhibiting no sensation or muscle activity below the injury. ﾃつ*One of the medical residents on staff, who happened to be assisting Dr. De la Torre in his study of the effects of DMSO, quickly administered an intravenous infusion of DMSO. ﾃつ*Within two hours of receiving the IV, this quadriplegic patient began moving his toes. ﾃつ*Incredibly, he later left the hospital with full function.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*This was a unique case, both because DMSO was administered so quickly and the patients recovery was so miraculous and unprecedented. ﾃつ*It was widely reported in the Chicago newspapers, but not one spinal surgery or trauma center took interest to follow up on this case or study DMSO as a therapy for spinal cord injury.
DMSO Should Be An Adjunct Treatment
ﾃつ*ﾃつ*ﾃつ*ﾃつ*DMSO is also highly effective in the treatment of closed head trauma (the type of head injury resulting from a car accident or blow to the head) and can prevent some of it's neurological consequences, as well. ﾃつ*Currently large doses of steroids are the treatment of choice for both spinal cord and head injury. ﾃつ*The addition of DMSO to that protocol would in no way interfere with current therapies, as steroids and DMSO function quite differently. ﾃつ*Because DMSO is exceptionally safe, and it's potential benefits have been demonstrated in animal studies and in very limited use in humans - and because these injuries have such tragic consequences - I strongly feel that DMSO should immediately be elevated to conventional use.
ﾃつ*ﾃつ*ﾃつ*ﾃつ*Would Christopher Reeve have been helped with infusions of DMSO immediately after his injury? ﾃつ*Difficult to say. ﾃつ*Should he have been given DMSO immediately after his injury? ﾃつ*In my opinion, based on existing literature and it's excellent safety record, unequivocally yes.
Interesting Curtis, most of the studies regarding the use of DMSO in acute injuries are from the early 80's so a lot of the abstracts aren't available but I did find the following:
Neurol Res 1988 Dec;10(4):232-5
Effects of methyl prednisolone, dimethyl sulphoxide and naloxone in experimental spinal cord injuries in rats.
Zileli M, Ovul I, Dalbasti T.
Aegean University, Faculty of Medicine, Department of Neurosurgery, Bornova, Izmir, Turkey.
The effects of methyl prednisolone (MPD), dimethyl sulphoxide (DMSO), and naloxone were examined in 38 albino rats after making an impact spinal cord injury on the midthoracic segments with a modified Allen's weight dropping trauma method. Somatosensorial evoked potentials (SEPs) were recorded before and 12 h and 14 d after the injury from epidurally inserted electrodes on the parietal cortex with sciatic nerve stimulations. Lower extremity motor functions of the animals were also examined. It may be concluded that in this study model, DMSO has a moderate effect which can be demonstrated clinically and through SEPs. Naloxone has no effect on the clinical outcome but causes reasonable improvement electrophysiologically.
Res Vet Sci 1979 Sep;27(2):253-5
Lack of functional recovery from spinal cord trauma following dimethylsulphoxide and epsilon amino caproic acid therapy in dogs.
Parker AJ, Smith CW.
The spinal cords of 20 normal dogs were exposed via dorsal laminectomies at L1 and damaged with a direct impact force of 440 g cm. One hour later treatment with dimethylsulphoxide (DMSO) was started on 10 dogs and with epsilon amino caproic acid (EACA) on the other 10 dogs. Administration of the DMSO ceased at 41 h after trauma and EACA at 49 h. The results showed that neither drug had a significant beneficial effect on the functional recovery of the spinal cords, when compared to a control group of similarly traumatised dogs.
Surg Neurol 1980 Apr;13(4):273-6
The effect of dimethyl sulfoxide on gray matter injury in experimental spinal cord trauma.
Goodnough J, Allen N, Nesham ME, Clendenon NR.
The possible effect of dimethyl sulfoxide upon the development of lesions in the gray matter after experimental spinal cord trauma has been investigated with the use of cytochrome oxidase assay and quantitative histologic measurement of total liquefaction necrosis. Observations were made in 17 unconditioned dogs receiving an impact trauma of 400 gm cm force. Experimental animals were given 2.5 gm/kg of dimethyl sulfoxide in 40% solution intravenously one hour prior to trauma, and control animals received a similar volume of saline. No reduction could be found in the degree of loss of cytochrome oxidase at one hour after trauma, nor in the extent of acute necrosis. A slight but non-significant increase in the amount of hemorrhage was noted in gray matter at the trauma site following treatment with dimethyl sulfoxide. The agent resulted in an increase in cytochrome oxidase activities in nontraumatized control gray matter.
J Korean Med Sci 1998 Dec;13(6):638-44
Failure of topical DMSO to improve blood flow or evoked potentials in rat spinal cord injury.
Park YK, Tator CH.
Department of Neurosurgery, Korea University Guro Hospital, Seoul. firstname.lastname@example.org
Dimethyl sulfoxide (DMSO) is a well-known hydroxyl radical scavenger, which is readily absorbed through biological membranes. We studied the effects of locally applied DMSO on acute spinal cord injury. Either 10% DMSO in saline (n=8) or saline alone (n=7) was applied directly to the exposed cervical spinal cord of rats 1 hour after clip compression injury of 26 g force for 1 minute. The outcomes measured were spinal cord blood flow and evoked potentials. Spinal cord blood flow was not significantly different between these two groups. Although the evoked potentials showed spontaneous recovery after injury, there was no significant difference between the groups. In this study we failed to show any beneficial effects from topical application of high-dose DMSO on spinal cord blood flow or evoked potentials after acute spinal cord injury.
Indian J Exp Biol 1992 Jun;30(6):509-11
Evaluation of drug effects on spinal cord injury--an experimental study in monkeys.
Cherian L, Kuruvilla A, Abraham J, Chandy M.
Department of Pharmacology, Christian Medical College and Hospital, Vellore, India.
Contusion injury is produced experimentally in anaesthetised monkeys by weight drop method. A group of animals having laminectomy alone served as sham controls. Drugs were administered 30 min after injury initially. Naloxone and nifedipine were administered as single dose administration immediately after injury. Dipyridamole and DMSO were administered daily for a period of 1 week. Acetylcholinesterase (AchE) was estimated in 2 spinal tissue segments, S1-at the site of injury and S2-the segment above the site of injury, at the end of 1 week after sacrificing the animals. Contusion injury produced significant decrease in specific activity of AchE in the traumatised segment of the experimental animals. The non-traumatised adjacent segment did not show any significant change. Nifedipine, naloxone and DMSO produced a decrease in AchE activity in S1 and S2 segments. Monkeys developed paraplegia after contusion injury. A score 2+ was observed after 1 week as compared to the score of 4+ of sham controls. Single dose administration of naloxone seemed to reverse the motor deficit by getting a score of 3+; other drugs did not produce any beneficial effect on motor deficit.
Neurology 1975 Jun;25(6):508-14
Pharmacologic treatment and evaluation of permanent experimental spinal cord trauma.
De La Torre JC, Johnson CM, Goode DJ, Mullan S.
Permanent paralysis was induced in dogs by a 500 gram centimeter force injury on the spinal cord, and drug treatments were given 1 hour after injury and were continued for 3 days. Dogs were evaluated for 90 days. Isotonic saline or mannitol administration were ineffective in reversing the paralysis. In dogs receiving either dimethyl sulfoxide or dexamethasone, six of eight animals in the former and two of eight in the latter group regained partial or full recovery. The presence of somatosensory evoked responses taken before and at various intervals following trauma showed a good correlation in the prognostic recovery of each animal. It is concluded that dimethyl sulfoxide and dexamethasone can reverse a permanent experimental injury to the spinal cord when given within an hour after trauma.
Ann N Y Acad Sci 1975 Jan 27;243:362-89
Dimethyl sulfoxide in central nervous system trauma.
de la Torre JC, Kawanaga HM, Johnson CM, Goode DJ, Kajihara K, Mullan S.
Dimethyl sulfoxide has been tested in various experimental injuries of the central nervous system in relation to other therapies. It appears to be a useful drug in acute extradural mass-forming lesions, middle cerebral artery occlusion, respiratory anoxia, and spinal cord injuries, in rhesus and squirrel monkeys, dogs, and rats. The data from these studies suggest that in the experimental models used, DMSO is clearly superior to no treatment, and appears to be more generally effective than other comparable treatments. No satisfactory answer has yet been found to explain the beneficial effects of DMSO, but several hypothetical suggestions are offered; their validation hinges primarily on further confirmatory evidence. Further experiments with our present models and alternative research lines are discussed.
Ann Emerg Med 1985 Aug;14(8):816-21
Spinal cord injury and protection.
Anderson DK, Demediuk P, Saunders RD, Dugan LL, Means ED, Horrocks LA.
Subsequent to traumatic injury of the spinal cord, a series of pathophysiological events occurs in the injured tissue that leads to tissue destruction and paraplegia. These include hemorrhagic necrosis, ischemia, edema, inflammation, neuronophagia, loss of Ca2+ from the extracellular space, and loss of K+ from the intracellular space. In addition, there is trauma-initiated lipid peroxidation and hydrolysis in cellular membranes. Both lipid peroxidation and hydrolysis can damage cells directly; hydrolysis also results in the formation of the biologically active prostaglandins and leukotrienes (eicosanoids). The time course of membrane lipid alterations seen in studies of antioxidant interventions suggests that posttraumatic ischemia, edema, inflammation, and ionic fluxes are the result of extensive membrane peroxidative reactions and lipolysis that produce vasoactive and chemotactic eicosanoids. A diverse group of compounds has been shown to be effective in ameliorating spinal cord injury in experimental animals. These include the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS); the antioxidants vitamin E, selenium, and dimethyl sulfoxide (DMSO); the opiate antagonist naloxone; and thyrotropin-releasing hormone (TRH). With the exception of TRH, all of these agents have demonstrable antioxidant and/or anti-lipid-hydrolysis properties. Thus the effectiveness of these substances may lie in their ability to quench membrane peroxidative reactions or to inhibit the release of fatty acids from membrane phospholipids, or both. Whatever the mode of action, early administration appears to be a requirement for maximum effectiveness.
Undersea Biomed Res 1980 Dec;7(4):305-20
Therapeutic effects of hyperbaric oxygen and dimethyl sulfoxide following spinal cord transections in rats.
Gelderd JB, Welch DW, Fife WP, Bowers DE.
Thirty adult, male, Long-Evans hooded rats underwent spinal cord transections at the T5 vertebral level. Following surgery, animals were separated into three groups: Group I received only normal postoperative care; Group II received daily hyperbaric oxygen (HBO) treatments for 47-54 consecutive days; Group III received the same HBO treatment as Group II in addition to subcutaneous injections of dimethyl sulfoxide (DMSO) for 10 consecutive days. All animals were killed 60-70 days postlesion. The lesioned area of spinal cord was removed and prepared for light and electron microscopy. Group I animals showed typical scar reduction of cavitations, increased scarring, and more nerve fibers within the lesion. Three animals in this group exhibited coordinated hindlimb movement, with one animal showing weight-bearing ability. The lesion sit in group III animals revealed a reduction in collagen formation and a further increase in the number of nerve fibers. Six animals in Group III showed coordinated hindlimb movements; among these two displayed weight-bearing ability and sensory return.
Curtis, one of the problems in science is that negative results are often not pursued or studied so that one seldom gets closure on a treatment that does not work. I think that this was the case with DMSO. In the early 1980's, several laboratories reported animal studies suggesting that DMSO may be neuroprotective in spinal cord injury. These results were not replicated by other laboratories and most scientists in the field were not convinced by the results reported and did not work on that treatment. However, the drug was tried in patients by a number of centers. Actually, I did not know that it was used in Boston. I know that Barth Green tried DMSO on patients at Miami. To my knowledge and, again, this was not published, the treatment did not produce beneficial effects on any of the patients. There is some theoretical basis for a neuroprotective effect of DMSO. For example, it does scavenge free radicals and will penetrate into tissues. Unfortunately, most of the positive reports from the early 1980's were about preservation of chemical measures and not functional recovery. After the initial positive reports in the 1980's, there were no other positive reports of therapeutic effects from any of the major laboratories in the field and only scattered reports from overseas. Although it had been tried in people, none of the trials placebo-controlled and there has been no report of improvement in patients that did receive the drug. So, this is one of many treatments that have been in that limbo world of therapies that have not been definitively studied.
thanks Dr. Young and Seneca
I guess I must have been one of the few people that DMSO was tried on back then, thanks.
Can DMSO be used to piggy-back stem cells to damaged areas of the cervical spine?
Originally Posted by Wise Young
I know that DMSO is used for bone marrow transplants, and wondered if it could be used to carry autologous stem cells to damaged areas of C4 complete spinal cord injuries, in order to avoid the threat of causing more injury to the patient, and causing complications with breathing etc., since this seems to be the main concern to do stem cell studies on this population?
DMSO is mostly used to facilitate diffusion of drugs. There is no evidence that I know of that suggests that DMSO will facilitate migration of cells into the spinal cord whether given intravenously or intrathecally (into the cerebrospinal fluid surrounding the spinal cord). Wise.