DMSO et cerveau ( 2ème partie)
extrait de : https://www.midwesterndoctor.com/p/dmso-heals-blood-vessels-and-could?
Animal Hemorrhagic Stroke Studies
In experimental brain hemorrhages, DMSO given an hour after the bleed prevented the collapse of the brain’s antioxidant defenses and cut mortality to zero (vs. 25% in controls by three hours). In rats, it held lipid-peroxidation products at normal levels rather than letting them climb; in cats, it kept oxygen and glucose metabolism near baseline and blunted the flood of lactate an injured brain pours into the bloodstream. The authors doubted the improved flow was vasodilation as DMSO only widens vessels at 1%+ concentrations, well above those reached at 0.3 g/kg and attributed it instead to the compound’s antiedematous action: by raising blood osmolarity (335→352 mosm/L), DMSO drew fluid out of the swelling brain, an effect they compared to glycerol’s; the accompanying drop in brain lactate, they suggested, aided the same anti-edema process..1,2
The protection reaches the molecular level too: in hemorrhagic shock, another state where the brain loses its blood supply, DMSO quieted the inflammatory driver NF-kappaB while boosting the survival protein HSP70.
Note: much of this foundational Russian work on DMSO in acute intracerebral hemorrhage is collected in a dedicated chapter (by M.B. Plotnikov) of a Russian monograph on DMSO in clinical practice.1 Interestingly, much of Plotnikov’s later work (I just came across and need to read in detail) revolved around the hypothesis that increased blood viscosity (which included oxidized red blood cells clumping together, and after ischemia–reperfusion injuries occurred were further oxidized) was not only a marker but an amplifier of many diseases, particularly high blood pressure, chronic cerebrovascular disease, brain ischemia, and ischemic heart disease, and to a lesser extent venous insufficiency, diabetes, radiation injury, and shock—dovetailing with my understanding of the subject. As he worked in a Soviet/Russian cerebral-pharmacology and viscometry tradition he appears not to have engaged with the Western blood-sludging or zeta-potential or microstroke research, and hence arrived at a variety of different disease and treatment insights than what I’ve come across.
Human Hemorrhagic Stroke Studies
•In a study of 11 patients with dangerously high ICP and Glasgow Coma Scores of 4–6 following brain trauma, encephalitis or subarachnoid hemorrhage (patients on the verge of death for whom standard therapy had failed), IV DMSO (1 g/kg) promptly lowered ICP (mean drop ~23 mm Hg at 30 min) and produced a brisk diuresis. Three patients survived with good functional recoveries; the others died despite ICP control. Unlike barbiturates, which lower systemic arterial pressure and force patients into a coma, DMSO did neither—so cerebral perfusion pressure rose as ICP fell and patients remained clinically examinable.
•A second paper reported on nine patients who suffered partial or total paralysis after surgical repair of a ruptured aneurysm and had remarkable responses to DMSO:
A 61-year-old man developed left-sided paralysis after surgery; within 30 minutes of starting DMSO his cerebral blood flow rose and he improved markedly. When DMSO was stopped on day 5 the paralysis and confusion rapidly returned—and resolved again once it was resumed, after which he fully recovered.
A 67-year-old woman who lost speech and developed right-sided paralysis (and hadn’t responded to mannitol) became fully alert and regained her strength within 45 minutes of DMSO; her motor function permanently normalized within 12 hours.
A 25-year-old woman who developed right-leg paralysis and speech difficulty 12 days after aneurysm surgery, again after mannitol failed, could lift her leg within 90 minutes of DMSO and had fully recovered by the next day.
A 28-year-old woman with an MCA aneurysm and a severe carotid spasm unresponsive to standard care recovered completely on DMSO.
The remaining five cases followed the same course, with all but one (who had severe complicating factors) making a full recovery. No adverse events occurred in any case.
In de la Torre’s own book,1 IV DMSO for ruptured aneurysms in humans is likewise reported to reverse progressive hemiplegia, relieve vasospasm and the resulting low cerebral blood flow, and improve motor deficits.
Hemorrhages Elsewhere in the Body
That DMSO limits bleeding is not unique to the brain—it has been observed in other organs, indicating this is a general property of DMSO. In a pig model of myocardial ischemia-reperfusion, intracoronary DMSO essentially eliminated intramyocardial hemorrhage (0 of 8 DMSO animals vs. 7 of 7 controls by cardiac MRI, and 1 of 10 vs. 8 of 8 by pathology) and reduced microvascular obstruction by 45%, with no hemodynamic or arrhythmic side effects.1 A Russian literature review likewise lists hemorrhages among the conditions DMSO (with antibiotics) is applied to directly, alongside bruises, sprains, and edema.1 Finally, in children with hemophilia, topical DMSO has been used as part of physiotherapy protocols for acute joint bleeding (hemarthrosis)—applied for 2–4 days to relieve pain, prevent intra-articular clotting, and reduce the progression toward joint damage.1,2
Hemorrhagic Stroke Combinations
As before, many agents have been combined with DMSO here and demonstrated efficiacy for intracerebral and subarachnoid hemorrhages, many of which targeting the same injury cascades DMSO itself acts on (e.g, oxidative stress, inflammation, blood-brain barrier breakdown, edema, vasospasm, and neuronal death).
Natural agents — curcumin⬖ (reduced brain-cell death and mortality, protected the blood-brain barrier and reduced swelling, and outperformed nimodipine against vasospasm)1,2,3; resveratrol⬖ (improved neurological outcomes and reduced cell death, swelling, and inflammation)1,2,3; 6-gingerol⬖ (improved neurological function and reduced swelling, cell death, and inflammatory cytokines)1; quercetin⬖ (reduced oxidative stress, cell death, swelling, and vasospasm)1; allicin⬖ (improved neurological outcomes and protected the blood-brain barrier)1; honokiol⬖ (reduced cell death and improved cognition)1; genistein⬖ (reduced inflammation and improved neurological outcomes)1,2,3; sulforaphane⬖ (improved outcomes)1,2; EGCG⬖ (green-tea polyphenol; reduced oxidative injury and cell death)1; naringenin⬖ (improved neurological outcomes and reduced inflammation)1; piperine⬖ (relieved vasospasm)1; triptolide⬖(reduced cell death and inflammation)1; salvinorin A⬖ (relieved vasospasm)1,2; schisandrin A⬖ (reduced pyroptosis, an inflammatory form of cell death) 1; astragaloside (A and IV)⬖ (improved neurological outcomes and reduced vasospasm)1,2; anethole trithione (a hydrogen-sulfide donor; reduced inflammation) 1; omega-3 polyunsaturated fatty acids⬖ (improved outcomes and increased protective autophagy)1.
A parallel set of targeted pathway inhibitors and drugs dissolved in DMSO also hemorrhagic reduced brain injury:
Cell-death pathway inhibitors — necroptosis inhibitor1,2,3,4,5; caspase-1 inhibitor1; caspase-3 inhibitor1,2,3; ferroptosis inhibitor1,2; necrosulfonamide1; caspase inhibitor1.
Kinase, signaling & channel inhibitors — ERK inhibitor1,2,3; p38 MAPK inhibitor1,2,3; JNK inhibitor1; HIF-1α inhibitor1,2,3,4; LRRK2 inhibitor1,2; STING inhibitor1; PTEN inhibitor 1; PTP1B inhibitor1; HDAC inhibitor1; Drp1 inhibitor1; IRE1α inhibitor1; AP-1 inhibitor 1; TRPC channel blocker1; FAK inhibitor1,2; aquaporin-regulating ERK inhibitor1; valproate and related HDAC inhibitors (improved survival in hemorrhagic-shock and TBI models)1.
Iron, heme & inflammatory-pathway agents — TLR4 blocker1,2; heme oxygenase-1 inhibitor1,2; iron chelator1; mTOR inhibitor1,2; tin-mesoporphyrin, a heme oxygenase inhibitor1.
Receptor ligands, growth factors & neuropeptides — TSPO ligand1,2; FGF-21; mitoNEET ligand1; ghrelin1; IGF-11; orexin-A1; apelin-131; sufentanil1; siponimod1; recombinant neurotrophin-41.
Other drugs & compounds — mGluR1 antagonist1; cyclosporine A1,2; 2-methoxyestradiol1; dabigatran1; glibenclamide1; tamoxifen1; praeruptorin E1; didymin1; H₂S donor AP391; chelerythrine1; Nur77 modulator1; rosuvastatin and simvastatin (reduced tPA-related hemorrhage and infarct)1
Note: an emodin⬖ study in acute pancreatitis (DMSO alone as a solvent) reduced tissue hemorrhage scores as one marker.
DMSO in Interventional Neurosurgery
I have argued the reason many transformative medical therapies do not enter medical practice despite widespread public demand for them is because we exist within a “pay to play” system, where access to the mainstream medical marketplace can only be earned if massive amounts of money are spent to secure an FDA approval—which is problematic as approval is largely dependent upon the money spent, not the quality of the therapy (which is essentially why the medical medical marketplace is crowded with mediocre and harmful therapies).
A key piece of evidence for my contention is that while many of the transformative (but off-patent) therapies I have come across are effectively barred from mainstream care, once the therapy is repackaged into something far more expensive and proprietary, it is often a widely embraced therapy (e.g., while used globally with immense data behind it, ultraviolet blood irradiation is not permitted in American medicine, but UVBI combined with a photosensitizer—extracorporeal photopheresis—is a widely used and extremely expensive therapy here and likewise many proprietary DMSO containing drugs have been approved by the FDA).
So, while “unsafe” DMSO is not used for strokes despite fifty years of pleas and research—it simultaneously is. Specifically, a common way many blood vessel issues are addressed is by threading a catheter into an easy-to-reach artery (for example the groin or the wrist) and then guiding it through the vessels to the site of the problem and doing something there, such as placing a stent, so you do not have to open the body surgically to get to that spot.
One common reason this is done is to cut off blood flow in a vessel, for example a bleeding artery. One popular way to do that uses DMSO to dissolve a polymer that is not soluble in blood, thereby allowing it to stay liquid in the catheter, so it can be pushed to the target. However, once it is injected into the bloodstream, the DMSO diffuses away and the polymer precipitates into a cast that plugs the vessel and stops flow. As such, tens of thousands of published papers exist on this DMSO combination1,2,3 (with numerous readers sharing they recognized DMSO because it was in one of those agents).
Note: while generally safe1 (with an experienced operator), since very high concentrations of DMSO are used to dissolve the polymers, they have to injected slowly so the vessels and brain tissue are not injured by a highly concentrated burst of DMSO (whereas in contrast much lower DMSO concentrations are typically used in DMSO IVs). Additionally, since the polymer plugs can travel from the target site, side effects periodically happen (and comprise a significant portion of the small number of side effects which have been reported for DMSO—as all agents used at the time of an adverse event are typically reported).
Reader Hemorrhage Reports
My most impressive experience with DMSO has been post a hemorrhagic stroke my Father had due to anticoagulant use for atrial fibrillation. Free iron from hemorrhage, especially in the brain, is quite possibly the most inflammatory event that can happen and responds to DMSO.
After IV DMSO he was totally mentally restored in 4 hours, sitting up in bed asking what his Dr said about his condition and was discharged in 36 hours with NO complications!! — From a physician reader
Several readers have described applying DMSO in the immediate aftermath of an aneurysm or brain bleed. The most detailed came from a reader whose 84-year-old mother suffered a grade 3 brain aneurysm and subarachnoid hemorrhage: about 90 minutes after the event, as paramedics loaded her into the ambulance, the reader applied topical DMSO, with a smaller application in the ER hours later and small amounts perhaps six times over the next two weeks in the ICU. She went on to make a nearly complete—possibly complete—neurological recovery, with her remaining issues (weakness, UTIs) plausibly attributable to six weeks of bed rest. The reader described her recovering in sudden increments, as if her brain were “re-indexing” visual and motor skills and finding neural pathways that had been misplaced after the aneurysm.1 In a follow-up roughly a year later, the same reader reported that despite a subsequent fall and subdural hematoma (during which DMSO was only applied several days late), his mother remained in assisted living with most of her cognitive function and mobility intact—an outcome he understood to be exceptional for someone her age.1
Another reader described her own nonaneurysmal brain hemorrhage following an ice bath, three weeks after first buying DMSO on the strength of these articles. Her partner applied DMSO immediately; she went to the hospital, then resumed topical DMSO at home. At a follow-up scan, the neurosurgeon reportedly expressed surprise both that she had not developed cerebritis after the hemorrhage and that she had improved so markedly in such a short time.1
A reader whose 93-year-old grandmother had suffered several brain injuries over eighteen months—including a stroke and two brain bleeds caused by a fall with a blow to the head—reported that treating her with DMSO “made her recovery much faster.”1Another reader survived a brain hemorrhage three weeks after buying DMSO on the strength of these articles; after the hospital misdiagnosed her, she applied it topically and then took it orally twice a day, and came through with “no inflammation and very little residual issues.” In her words, “without [@MidwesternDoc] I don’t think I would be alive today.”1
A reader who purchased DMSO for her mother-in-law—who had suffered a brain aneurysm seven years earlier—noted improvements across a range of unrelated issues (plantar fasciitis, knee-replacement swelling, varicose veins, arthritic hands) and was watching to see whether cognition and brain fog would improve over time. In the same report, the reader’s husband, who suffered near-constant neck and head pain and worsening migraines, applied DMSO once and reported his headache and neck pain were “GONE.”1
DMSO’s ability to relieve the pressure a mass places on neural tissue was also illustrated in a non-hemorrhage case. A clinician reader who shared he’d seen several glioblastomas resolve with mebendazole described one patient left virtually blind in one eye because the tumor had compressed the optic nerve; even after eight months of treatment fully eliminated the tumor, the blindness remained. After being shown DMSO eye drops, the patient used them once—and by the next morning his wife reported his vision had returned to normal.1 Though the tumor was gone, the compressive injury to the nerve had persisted until DMSO addressed it, mirroring the way DMSO relieves the pressure and secondary injury that follow a brain bleed.
Likewise, another reader’s partner (aged 75) was diagnosed with an inoperable 8 cm glioblastoma causing a slow brain bleed, losing the ability to speak and developing right-side paralysis, with a prognosis of three weeks to live. After copious topical DMSO, motor function began returning within 24 hours; over the following weeks the partner regained the ability to feed himself, communicate using Google Translate, and perform basic activities, and by week four could walk with a walker. A new CT scan at day 55 showed no brain bleed and reduced tumor metrics.1
Collectively, these reports mirror what was reported within DMSO literature and again suggest (provided another anticoagulant is not being taken), DMSO does not expose individuals with an active brain bleed to a serious risk. That said, the far smaller number of hemorrhagic testimonials makes me less confident in this assessment (e.g., if someone had used DMSO for a hemorrhagic stroke and died I would not have heard from them and within a sample that small that possibility can’t be excluded). However, given that hemorrhagic strokes are much rarer than ischemic strokes (13% vs. 87%), even if every case where a reader had used DMSO for either type of stroke was reported to me, I would still expect to receive far less hemorrhagic stroke reports. Notably, the ratio between all the ischemic and hemorrhagic stroke reports I’ve received here is fairly close to their expected distribution within the population, again suggesting there is not a significant (hidden) pool of readers with bad DMSO hemorrhagic stroke experiences.
Traumatic Brain Injuries and Concussions
While ischemic strokes are difficult to treat, hemorrhagic strokes and severe traumatic brain injuries are often more challenging still, and after decades, progress in neurologic intensive care has been limited, particularly in preventing the long-term paralysis and disability that follow a serious head injury.1 The core problem is that the initial impact is only the beginning, as in the hours and days that follow, a secondary injury unfolds, as swelling raises the pressure inside the rigid skull, circulation to the injured tissue falls, free radicals are generated in large quantities, and cells that survived the initial trauma begin to die.
This secondary cascade, together with the impact itself, determines whether a patient lives, and whether they recover. DMSO addresses that cascade at almost every point at once. It rapidly draws off the excess fluid driving intracranial pressure, restores circulation to the compromised tissue, scavenges the free radicals generated by the injury, and directly protects neurons from dying. Because a traumatic brain injury requires all of these problems to be solved simultaneously (something conventional care attempts with a different intervention for each, with the therapies often having conflicting effects and hence requires careful balancing between them), an agent that does all of the needed actions together is uniquely suited to the task. What follows is the extensive and largely forgotten evidence that DMSO does here.
Note: conflicting evidence exists supporting the use of progesterone, hypothermia, andhyperbaric oxygen therapy for traumatic brain injuries, but none of these approaches are in widespread use. Strong evidence also supports the use of methylene blue but it also is rarely used. Finally, certain trials (e.g., with progesterone or with an adenosine kinase inhibitor) find those therapies work even better if combined with DMSO.
Severe Head Trauma
The most striking human evidence concerns DMSO’s ability to rapidly lower the dangerously high intracranial pressure (ICP) that follows severe head injury, an effect that repeatedly translated into improved survival and neurological recovery.
Note: typically agents that lower ICP also lower (necessary) cerebral perfusion. As DMSO instead protects both, it is hence uniquely suited for these situations (e.g., while pentobarbitone and DMSO lowered ICP comparably (a 66% versus 45% drop)—pentobarbitone dropped systolic pressure by an average of 20 torr while DMSO caused no such drop, preserving cerebral perfusion1).
A pivotal study on this followed ten patients with closed head trauma and severely elevated ICP (40 to 127 mmHg, against a normal 5 to 13 mmHg) who received IV DMSO. In most cases ICP began dropping within 30 minutes, falling on average 28 mmHg after 24 hours and 58 mmHg after six days, with the reduction in brain swelling confirmed by CT scans. At a six-day neurological assessment, six patients had mild or no impairment and two had moderate impairment (two eventually died of their injuries), and by three months seven had minimal to no impairment. No adverse effects from DMSO were observed.1,2,3 This study, in turn, built on an earlier report of ten patients with severe closed head injuries, where DMSO rapidly reduced ICP and increased cerebral perfusion without lowering systemic blood pressure, and again improved the neurological course and outcome.1
These results were replicated across other studies. In a prospective study of 10 patients with severe closed head injury, marked brain swelling, and Glasgow Coma Scale (GCS) scores of 6 or below, IV DMSO (given whenever ICP reached 25 mmHg) dropped ICP markedly within 10 minutes (mean maximum reduction of 23.5 mmHg), raised cerebral perfusion pressure as ICP fell, and produced no rebound; seven of ten survived, six without gross deficits.1 In 12 patients with traumatic brain injury and elevated ICP, IV DMSO (given on average twice) rapidly reduced ICP in 21 of 23 treatment sessions, with the non-responding sessions also failing to respond to mannitol or furosemide, and no effect on blood pressure or other side effects.1,2 Likewise, a trial of 35 patients with severe head injury undergoing emergency cranial surgery found IV DMSO controlled ICP in 75% of cases (versus 53% with standard therapy), and controlled it in half of the patients who had already failed conventional treatment.1
The speed of the effect impressed even DMSO’s contemporaries. At a 1980 Congressional hearing on DMSO,1 Dr. Stanley Jacob discussed Oregon data (published in 19831) on 11 patients with intracranial hypertension from mixed causes, 5–6 of whom were already unresponsive to barbiturates and mannitol (3 of the barbiturate nonresponders after head trauma). IV DMSO dropped ICP to the normal range within 3–5 minutes in all 11 and was repeated as needed to keep ICP below 20 mmHg with three patients expected to die recovered well. A further five patients started on DMSO earlier did markedly better than those given it only after other measures had failed.
Finally, a report discussed by Dr. de la Torre1 (which I could not locate) detailed five patients with closed head injuries and high ICP that rapidly fell with IV DMSO. A 1.5 year old with a GCS of 7 and ICP of 30 mmHg fully recovered over 3 weeks, and a 7 year old admitted with a GCS of 5 and ICP of 25 mmHg fully recovered after 8 weeks; the three others (aged 17 to 52 with GCS scores of 3 to 5, two with ICPs above 50 mmHg) initially responded but did not survive.
Note: an early and candid 1982 report by UC San Diego researchers captured both the promise and the practical problem with DMSO in this era. The authors found the drug “often initially successful in controlling ICP” and “occasionally effective when barbiturates have failed” (and noted the ICP drop was too rapid to be a simple diuretic effect, implying a distinct mechanism), but struggled with its administration, as concentrated DMSO could dissolve standard IV tubing and the large fluid volumes then used were poorly suited to a head-injured patient (making prolonged control of ICP challenging to calibrate). These were solvable problems as refined protocols were developed (e.g., later work used lower concentrations and different IV materials to avoid them), but at the time they blunted enthusiasm for a therapy that was otherwise working.1,2,3 Likewise, a 1981 NIOSH report documented that staff at San Francisco General Hospital developed headaches and nausea (likely due to concentrated dimethyl sulfide) while working in rooms with patients receiving high-dose IV DMSO for an experimental cerebral-edema protocol, and that the problem resolved once room ventilation was improved1—something which has required clinics offering IV DMSO to often have a “DMSO only day” and that could likely also be addressed with appropriate air filters.
DMSO’s use for traumatic high ICP is also recognized in veterinary medicine, where its edema and pressure-lowering effects have long been utilized in large animals. A 1991 veterinary review of IV DMSO for traumatic brain injury in horses describes its use to reduce cerebral edema, intracranial pressure, and anoxia (with a regimen used at Oregon State University given slowly, generally twice daily), noting that DMSO increases localized circulation and cortical vasodilation, reduces platelet aggregation and fibrin thrombus formation in small injured vessels, protects endothelium, and reduces elevated ICP.1 Likewise, in equine clinical guidance, IV DMSO is indicated for acute head trauma resulting in high intracranial pressure and cerebral edema,1 and in parallel, a broader review of DMSO in equine medicine covers its application to central nervous system trauma among other indications.1 Similarly, in one case report, a 10-month-old filly presenting in coma after severe skull-brain trauma, IV DMSO was given as part of aggressive supportive therapy,1 and an early proprietary DMSO formulation was evaluated in craniotomized (skull opened) dogs for its effects on cerebral edema and inflammation.1 In another, a 2-day-old Quarter Horse filly with perinatal asphyxia and hypoxic-ischemic encephalopathy, given DMSO as part of supportive care, recovered fully by discharge,1 and a goat with polioencephalomalacia treated with IV DMSO alongside corticosteroids and mannitol showed progressive neurologic improvement with MRI-confirmed resolution of the lesion.1
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