For Concussions/TBI

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While the current level of knowledge about mild traumatic brain injuries (concussions) and recovery from them far exceeds what it was even 5 years ago, there is still much to be learned.  It is now known that repeated concussions, or even repeated sub-concussive impacts to the head can have serious long-term consequences, but the exact mechanisms of the injury are still not understood.  Likewise, why everyone’s recovery from a single concussion is different and how best to recover is still emerging.  We do know that there is significant evidence that cooling the brain post-injury and during the recovery phase has many positive benefits and a growing number of individuals are finding that icing their head and neck with the Cryohelmet is effective at managing the common symptoms of a concussion.

The studies below are in no particular order and provide a sampling of research in the area of selective brain cooling for the treatment of concussions.

RECENT STUDIES ON THE USE OF THERAPEUTIC HYPOTHERMIA FOR THE BRAIN:

  1. Emergence of cognitive deficits after mild traumatic brain injury due to hyperthermia.These results indicate that brain temperature is an important variable for mTBI outcome and that mildly elevated temperatures at the time of injury result in persistent cognitive deficits. Importantly, cooling to normothermia after mTBI prevents the development of long-term cognitive deficits caused by hyperthermia. Reducing temperature to normothermic levels soon after mTBI represents a rational approach to potentially mitigate the long-term consequences of mTBI.
  2. It might be time to let cooler heads prevail after mild traumatic brain injury or concussion. The use of mild hypothermia and/or targeted temperature management has revolutionized neonatal neurocritical care, impacted the neurocritical care of comatose adults after cardiac arrest, and the care of patients with a variety of other acute neurological insults such as severe TBI, stroke, spinal cord injury and subarachnoid hemorrhage. If temperature control is important to mTBI and concussion, it could have a substantial impact on mTBI outcomes, and in a very high risk group for the occurrence of multiple concussions. This seminal work throws down the gauntlet on an important area of future investigation and one very worthy of answers as we capitalize on the golden age of TBI research.
  3. A novel head-neck cooling device for concussion injury in contact sports   Emerging research on the long-term impact of concussions on athletes has allowed public recognition of the potentially devastating effects of these and other mild head injuries. Mild traumatic brain injury (mTBI) is a multifaceted disease for which management remains a clinical challenge. Recent pre-clinical and clinical data strongly suggest a destructive synergism between brain temperature elevation and mTBI; conversely, brain hypothermia, with its broader, pleiotropic effects, represents the most potent neuro-protectant in laboratory studies to date. Although well-established in selected clinical conditions, a systemic approach to accomplish regional hypothermia has failed to yield an effective treatment strategy in traumatic brain injury (TBI). Furthermore, although systemic hypothermia remains a potentially valid treatment strategy for moderate to severe TBIs, it is neither practical nor safe for mTBIs. Therefore, selective head-neck cooling may represent an ideal strategy to provide therapeutic benefits to the brain.
  4. Evidence for the Therapeutic Efficacy of Either Mild Hypothermia or Oxygen Radical Scavengers after Repetitive Mild Traumatic Brain Injury – “Collectively, these findings indicate that even mild hypothermia or the blunting free radical damage, even when performed in a delayed period, is protective in repetitive mTBI.  In sum, the present study continues to confirm the damaging consequences of repetitive brain injury while suggesting that some of its damaging consequences can be targeted with relatively innocuous therapeutic approaches that include mild hypothermia.”
  5. Recent Advances and Future Directions of Hypothermia for Traumatic Brain Injury – Brain temperature management was performed mainly in young patients, and the outcome on discharge was favorable in patients who received brain temperature management. Particularly, patients who need craniotomy for removal of hematoma were a good indication of therapeutic hypothermia. Improvement of therapeutic outcomes with widespread temperature management in TBI patients is expected
  6. Rapid and selective cerebral hypothermia achieved using a cooling helmet – “This helmet delivers initial rapid and selective brain cooling and maintains a significant temperature gradient between the core and brain temperatures throughout the hypothermic period to provide sufficient regional hypothermia yet minimize systemic complications.”
  7. Effects of selective hypothermia on blood-brain barrier integrity and tight junction expression levels after intracerebral hemorrhage in rats – “Together, these data suggest that local hypothermia is an effective treatment for edema formation and BBB disruption via the upregulation of TJ proteins and the suppression of TNF-α and IL-1β.”
  8. Effects of therapeutic hypothermia on inflammasome signaling after traumatic brain injury – “Therapeutic hypothermia may protect the injured central nervous system by targeting the detrimental consequences of the innate immune response to injury.”
  9. Selective brain cooling by head and neck cooling is protective in severe traumatic brain injury – “In conclusion, the noninvasive SBC described here is a safe method of administering therapeutic hypothermia, which can reduce ICP and improve prognosis without severe complications in patients with severe TBI.”
  10. Local head and neck cooling leads to hypothermia in healthy volunteers – “Treatment with the cooling device was well tolerated by all participants. The technique had measurable effects on core body temperature (rectal) and tympanic temperature (may reflect temperature at the external ear and skin rather than intracranial). It can be considered as a simple therapeutic approach to patients with suspected stroke in the prehospital setting.”
  11. Posttraumatic brain hypothermia provides protection from sensorimotor and cognitive behavioral deficits. – “The present data demonstrate that moderate postinjury brain hypothermia can provide protection from sensorimotor and cognitive behavioral deficits as well as neuropathology in a model of traumatic brain injury associated with early neuronal and microvascular injury.”
  12. Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. – “Post-traumatic brain hypothermia significantly reduced the overall sum of necrotic cortical neurons”
  13. Neuroprotective mechanisms of hypothermia in brain ischaemia. – “Cooling can reduce primary injury and prevent secondary injury to the brain after insults in certain clinical settings and in animal models of brain insult. The mechanisms that underlie the protective effects of cooling – also known as therapeutic hypothermia – are slowly beginning to be understood.Hypothermia influences multiple aspects of brain physiology in the acute, subacute and chronic stages of ischaemia. It affects pathways leading to excitotoxicity, apoptosis, inflammation and free radical production, as well as blood flow, metabolism and blood-brain barrier integrity. Hypothermiamay also influence neurogenesis, gliogenesis and angiogenesis after injury. It is likely that no single factor can explain the neuroprotection provided by hypothermia, but understanding its myriad effects may shed light on important neuroprotective mechanisms.”
  14. A military-centered approach to neuroprotection for traumatic brain injury. – “Candidate therapies selected for research include drugs that are aimed at reducing the acute and delayed effects of the traumatic incident, stem cell therapies aimed at brain repair, and selective brain cooling to stabilize cerebral metabolism. Each of these efforts can also focus on combination therapies targeting multiple mechanisms of neuronal injury.”
  15. Forced convective head cooling device reduces human cross-sectional brain temperature measured by magnetic resonance: a non-randomized healthy volunteer pilot study – “Convective head cooling reduced MRS brain temperature and core brain was cooled.”
  16. Neuroprotection of Selective Brain Cooling After Penetrating Ballistic-like Brain Injury in Rats – “These results indicate that 34°C SBC is effective in protecting against acute brain damage and related neurological dysfunction.”
  17. Oligodendrocyte Vulnerability Following Traumatic Brain Injury in Rats: Effect of Moderate Hypothermia – “Therapeutic hypothermia may improve functional outcome by attenuating trauma-induced oligodendrocyte cell death, subsequent demyelination, and circuit dysfunction.”
  18. Mild Hyperthermia (heat) Worsens the Neuropathological Damage Associated with Mild Traumatic Brain Injury in Rats – “These neuropathological results demonstrate that relatively mild elevations in temperature associated with peri-traumatic events may affect the long-term functional consequences of mTBI. Because individuals exhibiting mildly elevated core temperatures may be predisposed to aggravated brain damage after mTBI or concussion, precautions should be introduced to target this important physiological variable.”
  19. Alterations in Blood-Brain Barrier Permeability to Large and Small Molecules and Leukocyte Accumulation after Traumatic Brain Injury: Effects of Post-Traumatic Hypothermia – “These results indicate that moderate brain injury produces temperature-sensitive acute, as well as more long-lasting vascular perturbations associated with secondary injury mechanisms.”
  20. Comparison of whole-body cooling and selective head cooling on changes in urinary 8-hydroxy-2-deoxyguanosine levels in patients with global brain ischemia undergoing mild hypothermia therapy – “Mild hypothermia therapy with whole-body cooling had a greater effect on the suppression of free radical production than selectivehead cooling. However, selective head cooling might be an appropriate indication for patients with circulatory instability after resuscitation, because it provides neuroprotection similar to that of whole-body cooling.”
  21. Selective Hypothermia in the Management of Traumatic Brain Injury
  22. Traumatic Brain Injury Battlefield and Intensive Care Rapid and Selective Cerebral Hypothermia Using an Integrated Head-Neck Stabilization and Cooling Helmet System – “Our pilot study demonstrated that the cooling head cover was effective in rapidly achieving brain cooling and establishing a favorable brain-to-body temperature gradient. Our overall goal is to significantly improve the outcome of brain injured military personnel by rapidly inducing moderate cerebral (28-32°C) hypothermia but mild systemic (32-35°C) hypothermia to maximize the neuro-protective potentials yet minimize the systemic hypothermia induced complications.”
  23. Preoperative-induced mild hypothermia attenuates neuronal damage in a rat subdural hematoma model. – ” In conclusion, hypothermia induced early may reduce neuronal cell damage in the reperfusion injury, which was induced after ASDH removal.”
  24. Therapeutic targeting of the axonal and microvascular change associated with repetitive mild traumatic brain injury. – “Following repetitive injury, cerebral vascular reactivity was dramatically preserved by either therapeutic intervention or the combination thereof compared to control group in which no intervention was employed. Similarly, APP density was significantly lower in the therapeutic intervention group compared in controls. Although the individual use of FK506 or hypothermia exerted significant protection, no additive benefit was found when both therapies were combined. In sum, the current study demonstrates that the exacerbated pathophysiological changes associated with repetitive mTBI can be therapeutically targeted.”
  25. Survey of brain temperature management in patients with traumatic brain injury in the Japan Neurotrauma Data Bank – “Appropriate thermoregulation of the brain for individual patients with various types of TBI are important.”
  26. Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review. – “he best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI (Glasgow Coma Scale score < or = 8) to decrease mortality and improve rates of good neurologic recovery. This treatment should be commenced as soon as possible after injury (e.g., in the emergency department after computed tomography) regardless of initial ICP, or before ICP is measured.”
  27. Effects of hypothermia on cerebral autoregulatory vascular responses in two rodent models of traumatic brain injury. – “These results clearly illustrate that TBI can alter the cerebral autoregulatory vascular response to sequentially induced hypotensive insult, whereas the use of post-traumatic hypothermia provides benefit.”
  28. Selective brain cooling increases cortical cerebral blood flow in rats. – “The cerebral vasodilatory response to hypothermia may explain its protective effects during and after cerebral ischemia.”