SPINAL CORD INJURY

 

HyperMED Isabel Martin - At 9 months age young Isabel was operated on for a Benign Tumour resulting in her becoming a T4 complete Spinal Cord Injury.

MRI prior to commencing at HyperMED dated 13-03-07

'Comparison is made with the last examination dated 10-10-05.

Again demonstrating the enhancing intraspinal lesion posteriorly in the spinal canal at the level of T4-T6. It is again seen to measure 2.8cm cranio caudal and 1cm AP. The T2 imaging again shows cord atrophy with hydromyelia from T1 to at least the inferior border of the lesion'

The Final Frontier - 'Repair and Functional Restoration'

 * Hyperbaric Oxygenation primes the body and provides a fertile neurovascular platform for mobilizing the patient’s own immune and circulating stem cell capacity whilst preparing the body for further stem cell implantation techniques.

 ** Hyperbaric Oxygenation activates dormant and inactive nerve cells, promotes plasticity hastening recovery.

 *** The final frontier in the treatment of complex degenerative neurovascular disorders including brain and spinal cord injury is focused on ‘repair and functional restoration’. This involves the use of growth factors including Neurotropic Cerebryolysin and Gangliosides (GM1 ganglioside is a glycosphingolipid) to promote axonal sprouting, activation of idling and non-functional neurons whilst promoting neovascularization (new capillary formation) of damaged areas. Research efforts to bridge spinal cord and brain cell lesions are also underway experimentally, using transplanted tissues and bridging devices.

HOWEVER the ultimate success in these reconstructive methods and efforts are directly dependent on tissue vitality (neurovascular integrity). Spinal Cord insult causes a cascade of secondary degeneration due to hypoxia (inadequate Oxygen) and pro-inflammatory cytokines, including IL1, IL6, Il7, MMP9, TNFa from glial cells

  • The resulting neuro-inflammation can lead to progressive glial and neuronal cell death.

  • In addition remains a chronic 'smoldering' (cytokine) inflammation in the CNS that may continue to affect the spinal cord microenvironment.

  • Pro-inflammatory cytokines can kill cells, but they are also important in mobilizing reparative and regenerative responses.

  • Further, cytokines can affect synaptic strength and synaptic plasticity, and in excess can contribute to maladaptive plasticity, including chronic pain.

  • The extent of neurovascular deterioration can be significantly diminished with Hyperbaric Oxygenation (HBOT) which 'expands the therapeutic window'.

 * American Journal Physiology - Heart and Circulatory Physiology (2005) Stem Cell Mobilization by Hyperbaric Oxygenation reports a single 2-hour exposure to HBOT at 2 ATA doubles circulating CD34+ progenitor stem cells (primordial cells targeted to salvage and restore damaged structures); and at approx. 40-hours HBOT: CD34+ cells increases eight fold - (800%).

 ** Approximately 20-30% of the body’s consumption of Oxygen occurs within 3-5% of the body mass – the brain and spinal cord structures (Jain 1995). These structures are extremely sensitive to Oxygen deficiency. Spinal injuries including acute spinal cord trauma and/or chronic degenerative compounding injury traumatize the integrity of the supporting blood vessels, resulting in partial or complete destruction of the blood supply (ischemia) and capillary network systems required to maintain that region.

 

  • Hyperbaric Oxygen (HBO) UP~REGULATES Circulating Stem Cells (CD34+), Growth Factors (VEGF, BDNF, GDNF), Anti-inflammatory Interleukins including IL4, IL10, IL12, IL13 and INFγ (positive feedback loop).

  • HBO DOWN~REGULATES Pro-inflammatory Interleukins IL1, IL2, IL6, IL8, MMP9 and TNFα.

HyperMED (Hooper) Submissions

Am J Phys Med Rehabil. 2019 Oct;98(10):914-920. doi: 10.1097/PHM.0000000000001225.

Hyperbaric Oxygen Improves Functional Recovery of the Injured Spinal Cord by Inhibiting Inflammation and Glial Scar Formation.

Zhou Y1, Dong QPan ZSong YSu PNiu YSun YLiu D.

BACKGROUND:

Inflammation and glial scar formation determine the recovery process after spinal cord injury. Hyperbaric oxygen is used as a rehabilitation therapy for various clinical diseases, including spinal cord injury. However, the relationship between hyperbaric oxygen therapy and inflammation or glial scar is not fully understood.

OBJECTIVE:

The aim of this study was to investigate the therapeutic effect and molecular mechanism of hyperbaric oxygen on spinal cord injury.

METHODS:

A total of 54 developing female Sprague-Dawley rats were randomly divided into sham group, spinal cord injury group, and hyperbaric oxygen group, with 18 rats in each group. The model of spinal cord injury was established using Allen's method. Hyperbaric oxygen therapy was administered once a day until the rats were killed.

RESULTS:

The results demonstrated inflammation and glial scar formation are involved in secondary spinal cord injury. After hyperbaric oxygen treatment, there was a notable improvement of the locomotor function in rats

 * Hyperbaric oxygen reduced the inflammatory reaction and glial scar formation by inhibiting inflammation-related factors iNOS and COX-2 and glial scar-related components GFAP and NG2. This process may be achieved by inhibiting AKT and NF-kB pathways.

CONCLUSIONS:

Hyperbaric oxygen effectively promotes the recovery of spinal cord injury by inhibiting inflammation and glial scar formation.

Life Sci. 2019 Jul 15;229:187-199. doi: 10.1016/j.lfs.2019.05.029. Epub 2019 May 17.

Hyperbaric oxygen therapy reduces apoptosis and dendritic/synaptic degeneration via the BDNF/TrkB signaling pathways in SCI rats.

Ying X1, Tu W1, Li S1, Wu Q1, Chen X1, Zhou Y1, Hu J1, Yang G2, Jiang S3.

Abstract

Spinal cord injury (SCI) is a serious neurological disease without efficacious drugs. Anti-apoptosis and suppressing dendritic/synaptic degeneration in the anterior horn are essential targets after SCI. Previous studies found that hyperbaric oxygen therapy (HBOT) significantly protected rats after SCI. However, its potential effects and mechanisms remain unknown. The BDNF/TrkB signaling pathways evidently contribute to the SCI recovery.

 * Currently, we mainly investigate the potential effects and mechanism of HBOT on anti-apoptosis and ameliorating impaired dendrites, dendritic spines and synapses after SCI. Establish SCI model and randomly divide rats into 5 groups. After SCI, rats were subjected to HBOT. ANA-12 is the specific inhibitor of BDNF/TrkB signal pathway. Changes in neurological deficit, neuronal morphology, apoptosis, protein expression and dendrite/synapse were examined by Basso-Beattie-Bresnahan (BBB) locomotor rating scale, Hematoxylin-eosin (HE) and Nissl staining, TUNEL staining, RT-PCR, Western blot, immunofluorescence and Golgi-Cox staining.

We found HBOT suppressed dendritic/synaptic degeneration and alleviated apoptosis, consistent with the increase of BDNF and TrkB expression and improved neurological recovery. In contrast to the positive effects of HBOT, inhibitor increased degeneration and apoptosis. Moreover, we observed that these HBOT-mediated protective effects were significantly inhibited by inhibitor, consistent with the lower expression of BDNF/TrkB and worse neurobehavioral state.

 ** These findings suggest that hyperbaric oxygen therapy ameliorates spinal cord injury-induced neurological impairment by anti-apoptosis and suppressing dendritic/synaptic degeneration via upregulating the BDNF/TrkB signaling pathways.

COMMENT: Tropomyosin receptor kinase B is the high affinity catalytic receptor for several neurotrophins, which are small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3).[5] As such, TrkB mediates the multiple effects of these neurotrophic factors, which includes neuronal differentiation and survival.  * Research has shown that activation of the TrkB receptor can lead to down regulation of the KCC2 chloride transporter in cells of the CNS.[7]

Phys Ther. 2019 Sep 2. pii: pzz125. doi: 10.1093/ptj/pzz125. [Epub ahead of print]

Combination Therapy With Hyperbaric Oxygen and Erythropoietin Inhibits Neuronal Apoptosis and Improves Recovery in Rats With Spinal Cord Injury.

Zhou Y1,2, Su P3, Pan Z4, Liu D3, Niu Y3, Zhu W3, Yao P3, Song Y3, Sun Y5.

BACKGROUND:

Apoptosis plays an important role in various diseases, including spinal cord injury (SCI). Hyperbaric oxygen (HBO) and erythropoietin (EPO) promote the recovery from SCI, but the relationship between apoptosis and the combination therapeutic effect is not completely clear.

OBJECTIVE:

The purpose of this study was to investigate the effects of HBO and EPO on SCI and the mechanisms that underlie their therapeutic benefits.

DESIGN:

The study was designed to explore the effects of HBO and EPO on SCI through a randomized controlled trial.

METHODS:

Sixty young developing female Sprague-Dawley rats were randomly divided into groups of 12 rats receiving sham, SCI, HBO, EPO, or HBO plus EPO. The SCI model was modified with the Allen method to better control consistency. HBO was performed for 1 hour per day for a total of 21 days, and EPO was given once per week for a total of 3 weeks. Both methods were performed 2 hours after SCI. Locomotor function was evaluated with the 21-point Basso-Beattie-Bresnahan Locomotor Rating Scale, an inclined-plane test, and a footprint analysis. All genes were detected by Western blotting and immunohistochemistry. The level of cell apoptosis was determined by Hoechst staining.

RESULTS:

The results showed that HBO and EPO promoted the recovery of locomotor function in the hind limbs of rats by inhibiting the apoptosis of neurons.

 * During this period, the expression of B-cell lymphoma/leukemia 2 protein (Bcl-2) increased significantly, whereas the expression of Bcl-2-associated X protein (Bax) and cleaved caspase 3 decreased significantly, indicating the inhibition of apoptosis.

 ** Meanwhile, the expression of G protein-coupled receptor 17 decreased, and that of myelin basic protein increased, suggesting that there may be a potential connection between demyelination and neuronal apoptosis.

LIMITATIONS:

The limitations of the study include deviations in the preparation of SCI models; lack of reverse validation of molecular mechanisms; absence of in vitro cell experiments; and, only one time point after SCI was studied.

CONCLUSIONS:

HBO and EPO treatments are beneficial for SCI, especially when the 2 therapies are combined.

Biomed Res Int. 2019 Feb 25;2019:3290894. doi: 10.1155/2019/3290894. eCollection 2019.

Review of the Current Knowledge on the Role of Stem Cell Transplantation in Neurorehabilitation.

Kamelska-Sadowska AM1, Wojtkiewicz J2, Kowalski IM1,3.

Author information

Abstract

The management involving stem cell (SC) therapy along with physiotherapy offers tremendous chance for patients after spinal cord injury (SCI), traumatic brain injury (TBI), stroke, etc. However, there are still only a limited number of reports assessing the impact of stem cells (SCs) on the rehabilitation process and/or the results of the simultaneous use of SC and rehabilitation. Additionally, since there is still not enough convincing evidence about the effect of SCT on humans, e.g., in stroke, there have been no studies conducted concerning rehabilitation program formation and expected outcomes. It has been shown that bone marrow-derived mesenchymal stem cell (BMSCs) transplantation in rats combined with hyperbaric oxygen therapy (HBO) can promote the functional recovery of hind limbs after SCI. An anti-inflammatory effect has been shown. One case study showed that, after the simultaneous use of SCT and rehabilitation, an SCI patient progressed from ASIA Grade A to ASIA Grade C. Such promising data in the case of complete tetraplegia could be a breakthrough in the treatment of neurologic disorders in humans. Although SCT appears as a promising method for the treatment of neurological conditions, e.g., complete tetraplegia, much work should be done towards the development of rehabilitation protocols.

Improving sperm viability after spinal cord injury using hyperbaric therapy.

World Neurosurg 2018 Feb 9. Epub 2018 Feb 9.​

Background: Infertility is one of many complications of spinal cord injury (SCI) in male patients who are often at the peak of their reproductive life. This study evaluated the effects of hyperbaric therapy (HT) on the quality of sperm of rats submitted to SCI, correlating the findings with a histological analysis of the testicles.
Methods: Randomized experimental study in animals. Eighteen rats were submitted to SCI with a MASCIS Impactor and randomly allocated to either a HT or a control group. Testicular biopsies were performed on the first and 28day of the study, and four parameters were evaluated: concentration of sperm per mL, number of round cells per field, number of inflammatory cells per field (peroxidase-Endtz test), and sperm viability (HOS test).
Results: There was no difference in the sperm concentration between the HT group (P=0.41) and the control group (P=0.74) during the 28 days. From day 1 to day 28, sperm viability decreased twice as much in the control group (P=0.001) than in the HT group (P=0.017). There was no difference in mean sperm concentration, number of round and inflammatory cells between the groups. On the first day, there was no difference in sperm viability between groups. There was a significantly higher (P=0.001) percentage of viable sperm in the HT group (86.8±5.6) than in the control group (48.8±21.8) on the 28day.

  • Conclusions: SCI increased the number of round and inflammatory cells, and diminished sperm viability in both groups. HBOT promoted greater sperm viability in rats with SCI.

Med Gas Res. 2017 Jun 30;7(2):133-143. doi: 10.4103/2045-9912.208520. eCollection 2017 Apr-Jun.

Hyperbaric oxygen therapy of spinal cord injury.

Patel NP1, Huang JH1,2.

Author information

Abstract

Spinal cord injury (SCI) is a complex disease process that involves both primary and secondary mechanisms of injury and can leave patients with devastating functional impairment as well as psychological debilitation. While no curative treatment is available for spinal cord injury, current therapeutic approaches focus on reducing the secondary injury that follows SCI. Hyperbaric oxygen (HBO) therapy has shown promising neuroprotective effects in several experimental studies, but the limited number of clinical reports have shown mixed findings. This review will provide an overview of the potential mechanisms by which HBO therapy may exert neuroprotection, provide a summary of the clinical application of HBO therapy in patients with SCI, and discuss avenues for future studies.

Clin Biochem. 2018 Mar;53:1-7. doi: 10.1016/j.clinbiochem.2017.12.001. Epub 2017 Dec 5.

Hyperbaric oxygen ameliorated the lesion scope and nerve function in acute spinal cord injury patients: A retrospective study.

Tan JW1, Zhang F2, Liu HJ1, Li Z3.

OBJECTIVE:

This is a retrospective study to assess the therapeutic effect of hyperbaric oxygen (HBO) in early treatment of acute spinal cord injury (SCI) using magnetic resonance imaging (MRI) and electrophysiology in diagnosing.

METHODS:

Forty acute SCI patients from Sun Yat-Sen Memorial Hospital who were assigned into HBO treatment were included during August 2013 to October 2014.The patients with adverse reactions or contraindications for HBO were assigned as controls. Both of two groups (HBO and Control) received medicine treatment with Urbason, GM-1 and mecobalamine after surgery. ASIA and the Frankel scores were used to evaluate the therapeutic effect of HBO at the 15th and 30th day after HBO treatment by using MRI and electrophysiology features.

RESULTS:

Significant therapeutic effect of HBO treatment on acute SCI patients was observed compared with the control group (P<0.05). Comparison for ASIA and Frankel scores showed that motor and neurological functions were significantly improved in HBO group at day 15 and day 30 post treatment. MRI images showed that the grade III injury in HBO group was significant lower than the control group.

 * In comparison with the control, the peak of somatosensory evoked potential (SEP) and motor evoked potential (MEP) amplitude increased, the latency was shortened, and the conduction velocity of sensory nerve (SCV) and motor nerve (MCV) was significantly increased in the HBO group (P<0.05).

CONCLUSIONS:

HBO treatment has a great efficacy in acute SCI patients. HBO therapy at early stage of acute SCI is beneficiary to the recovery.

Mol Pain. 2017 Jan-Dec;13:1744806917730254. doi: 10.1177/1744806917730254.

Kindlin-1 is a key protein in hyperbaric oxygen therapy for the treatment of neuropathic pain.

Zhao B1, He E2, Pan Y1, Xu H1, Song X.

Abstract

BACKGROUND:

Hyperbaric oxygen therapy is increasingly used in adjuvant therapies to treat neuropathic pain. However, the specific targets of hyperbaric oxygen treatment in neuropathic pain remain unclear. Recently, we found that hyperbaric oxygen therapy produces an antinociceptive response via the kindlin-1/wnt-10a signaling pathway in a chronic pain injury model in rats.

METHODS:

The rats received an intraperitoneal injection of AAV-FERMT1 or an adeno-associated virus control vector 20 days before the chronic constriction injury operation. During five consecutive days of hyperbaric oxygen treatment, mechanical withdrawal threshold and thermal withdrawal latency tests were performed. Then, kindlin-1 expression was examined by real-time polymerase chain reaction and Western blot analysis. Meanwhile, the activation of glial cells and the production of TNF-α, IL-1β, and fractalkine were also determined.

RESULTS:

Our findings demonstrated that hyperbaric oxygen therapy inhibited the chronic constriction injury–induced increase in kindlin-1 expression.

 * Furthermore, overexpression of kindlin-1 reversed the antinociceptive effects of hyperbaric oxygen therapy.

 ** The observed hyperbaric oxygen–induced reductions in glial cell activation and neuroinflammation, as indicated by the production of TNF-α, IL-1β, and fractalkine, were also prominently diminished in the group with kindlin-1 overexpression.

CONCLUSIONS:

Our findings demonstrate that kindlin-1 is a key protein in the action of hyperbaric oxygen therapy in the treatment of neuropathic pain. Indeed, interference with kindlin-1 may be a drug target for reducing the neuroinflammatory responses of the glial population in neuropathic pain.

Smouldering Cytokine Storm Associated With Spinal Cord Injury

Degeneration, repair, and plasticity after SCI: A central role for cytokines (2015)

  1. Michael Beattie1, Adam Ferguson1 and Jacqueline Bresnahan1

Abstract

Spinal cord injury (SCI) induces a secondary injury process that releases pro-inflammatory cytokines, including TNFa from glial cells.

The resulting neuroinflammation sends signals to the periphery to recruit immune cells that invade the lesion cite, causing additional inflammatory responses that can lead to glial and neuronal cell death. This acute innate response to injury is followed by compensatory anti-inflammatory signals that dampen the initial response.

However, there remains a chronic 'smoldering' inflammation in the CNS that may continue to affect the spinal cord microenvironment. 

Pro-inflammatory cytokines can kill cells, but they are also important in mobilizing reparative and regenerative responses. Further, cytokines can affect synaptic strength and synaptic plasticity,and in excess can contribute to maladaptive plasticity, including chronic pain.

This lecture will review some of the literature on the balance between degeneration and repair mediated by TNF, and present data from our group on attempts to modulate TNFa in the acute and chronic phases of SCI, and their effects on neuronal and glial survival, and on spinal cord adaptive and maladaptive plasticity. Although the situation is complex, it seems clear that optimizing pro-inflammatory cytokine production both in the CNS and in the periphery remains an important therapeutic target not only in the acute phase, but also in chronic SCI.

The discovery and optimization of cytokine-directed therapies may also be aided by the use of multivariate approaches to the design and analysis of preclinical discovery platforms. Work reported here was supported by grants from the NIH (NINDS, NIA), the C.H.Neilsen Foundation, and the US Department of Defense.

Protective Effects of HBO After SCI (China 2014)

  • HBO treatment following SCI in rats exerts a protective effect by suppression of inflammation and cytokine release mitigating inflammation and resultant tissue damage, while promoting the recovery of locomotor function.

  • The proinflammatory cytokines IL-1β and TNF-α mediate SCI-induced inflammation. HBO also inhibited expression of IL-6, matrix metalloproteinase-2 (MMP-2), and MMP-9. HBO reduced inflammatory responses cell necrosis. HBO reduced SCI-induced spinal cord edema, stabilized the blood–spinal cord barrier, and promoted recovery of neuronal function by down regulating the expression of IL-6, MMP-2, and MMP-9 and up regulating the expression of VEGF (Vascular Endotheial Growth Factors).

Scand J Pain. 2017 Sep 15. pii: S1877-8860(17)30186-6. doi: 10.1016/j.sjpain.2017.08.014. [Epub ahead of print]

Hyperbaric oxygenation alleviates chronic constriction injury (CCI)-induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord.

Fu H1, Li F1, Thomas S2, Yang Z3.

Author information

Abstract

BACKGROUND AND AIMS:

Dysfunction of GABAergic inhibitory controls contributes to the development of neuropathic pain. We examined our hypotheses that (1) chronic constriction injury (CCI)-induced neuropathic pain is associated with increased spinal GABAergic neuron apoptosis, and (2) hyperbaric oxygen therapy (HBO) alleviates CCI-induced neuropathic pain by inhibiting GABAergic neuron apoptosis.

METHODS:

Male rats were randomized into 3 groups: CCI, CCI+HBO and the control group (SHAM). Mechanical allodynia was tested daily following CCI procedure. HBO rats were treated at 2.4 atmospheres absolute (ATA) for 60min once per day. The rats were euthanized and the spinal cord harvested on day 8 and 14 post-CCI. Detection of GABAergic cells and apoptosis was performed. The percentages of double positive stained cells (NeuN/GABA), cleaved caspase-3 or Cytochrome C in total GABAergic cells or in total NeuN positive cells were calculated.

RESULTS:

HBO significantly alleviated mechanical allodynia. CCI-induced neuropathic pain was associated with significantly increased spinalapoptotic GABA-positive neurons. HBO considerably decreased these spinal apoptotic cells. Cytochrome-C-positive neurons and cleaved caspase-3-positive neurons were also significantly higher in CCI rats. HBO significantly decreased these positive cells. Caspase-3 mRNA was also significantly higher in CCI rats. HBO reduced mRNA expression of caspase-3.

CONCLUSIONS:

CCI-induced neuropathic pain was associated with increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord. HBO alleviated CCI-induced neuropathic pain and reduced GABAergic neuron apoptosis. The beneficial effect of HBO may be via its inhibitory role in CCI-induced GABAergic neuron apoptosis by suppressing mitochondrial apoptotic pathways in the spinal cord.

IMPLICATIONS:

Increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord is critical in CCI-induced neuropathic pain. The inhibitory role of HBO in GABAergic neuron apoptosis suppresses ongoing neuropathic pain.

Hyperbaric Oxygen in the treatment of cerebral stroke, brain trauma, spinal cord injury and neurologic disease

Neural Regen Res. 2014 Dec 15;9(24):2182-8. doi: 10.4103/1673-5374.147951.

Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury.

Wang Y1, Zhang S2, Luo M1, Li Y3.

Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats.

 * Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury.

Adv Ther. 2005 Nov-Dec;22(6):659-78.

Life Support Technologies, Inc., and NewTechnologies, Inc., The Mount Vernon Hospital, Westchester Medical Center, New York Medical College, New York, USA.

Abstract

Hyperbaric Oxygen (HBO) therapy has been used to treat patients with numerous disorders, including stroke. This treatment has been shown to decrease cerebral edema, normalize water content in the brain, decrease the severity of brain infarction, and maintain blood-brain barrier integrity. In addition, HBO therapy attenuates motor deficits, decreases the risks of sequelae, and prevents recurrent cerebral circulatory disorders, thereby leading to improved outcomes and survival.

Hyperbaric Oxygen also accelerates the regression of atherosclerotic lesions, promotes antioxidant defenses, and suppresses the proliferation of macrophages and foam cells in atherosclerotic lesions. Although no medical treatment is available for patients with cerebral palsy, in some studies, HBO therapy has improved the function of damaged cells, attenuated the effects of hypoxia on the neonatal brain, enhanced gross motor function and fine motor control, and alleviated spasticity.

In the treatment of patients with migraine, HBO therapy has been shown to reduce intracranial pressure significantly and abort acute attacks of migraine, reduce migraine headache pain, and prevent cluster headache. In studies that investigated the effects of HBO therapy on the damaged brain, the treatment was found to inhibit neuronal death, arrest the progression of radiation-induced neurologic necrosis, improve blood flow in regions affected by chronic neurologic disease as well as aerobic metabolism in brain injury, and accelerate the resolution of clinical symptoms.

  • Hyperbaric Oxygen has also been reported to accelerate neurologic recovery after spinal cord injury by ameliorating mitochondrial dysfunction in the motor cortex and spinal cord, arresting the spread of hemorrhage, reversing hypoxia, and reducing edema. HBO has enhanced wound healing in patients with chronic osteomyelitis.

The results of HBO therapy in the treatment of patients with stroke, atherosclerosis, cerebral palsy, intracranial pressure, headache, and brain and spinal cord injury are promising and warrant further investigation.

Summary Effects Of Hyperbaric Oxygenation After Spinal Cord Injury (De la Torre 1981)

  • HBO elevates the patients own circulating stem cells

  • HBO can reverse neuronal damage that is due to bruising rather than laceration

  • HBO activates recoverable idling and dormant neurons in the penumbra zone (where there is diminished tissue Oxygenation) surrounding infarct cells

  • HBO relieves ischemia of the grey matter of the spinal cord

  • HBO reduces edema of the white matter (IL1, 2, 6, 8 & TNF)

  • HBO increases pO2 levels in the cerebral spinal fluid dynamics

  • HBO corrects biochemical disturbances at the immediate and distal sites of spinal cord injury including metabolic enzymatic disturbance

  • HBO stabilizes the negative impact of metabolic disturbances. This includes the production of free radicals capable of causing vasodilatation and vascular wall damage. Hypoxia (Oxygen starvation) causes a shift in glycolysis with the production of lactic acid and lowered pH levels. An imbalance of energy demand and availability results in further ischemic like state with loss of ATP available to the neurons and surrounding tissue. In addition to oxidative free radicals, excitatory amino acids are released as a consequence of vascular injury. The loss of cellular integrity and edema, combined with continuing biochemical toxic effects results in further ischemia, swelling and compression

  • HBO can minimize and even reverse secondary cascade degenerative spinal cord effects

 

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1141-53. eCollection 2015.

Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via regulation of HMGB1/TLR4/NF-κB signaling pathway.

Kang N1, Hai Y1, Yang J2, Liang F2, Gao CJ2.

Author information

Abstract

BACKGROUND:

To investigate whether hyperbaric oxygen (HBO) intervention affects the expressions of inflammatory cytokines, HMGB1/TLR4/NF-κB, and arrests secondary spinal cord injury (SCI).

METHODS:

One hundred and twenty healthy adult SD rats were randomly divided into four groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was then randomly divided into five subgroups of 6 rats each according to the following time points: 1, 2, 3, 7, and 14 d post injury. Functional recovery of the hindlimb was assessed by Basso, Beattie, and Bresnahan (BBB) scores at different time points after SCI. The expression of HMGB1, TLR4, and NF-κB in the spinal cord tissue was determined by fluorescence quantitative PCR, western blot, immunohistochemistry, and ELISA.

RESULTS:

The gene expressions of TLR4, HMGB1, and NF-κB (P < 0.01) and the TLR4 protein expression were significantly high after SCI. HBO intervention significantly decreased all the four parameters at 3, 7, and 14 d post injury (P < 0.05). A significant positive correlation (P < 0.01) was observed between the following: HMGB1 mRNA, TLR4 mRNA and TLR4 protein; HMGB1 mRNA and NF-κB mRNA; and TLR4 protein and NF-κB mRNA. BBB score was negatively correlated with HMGB1, TLR4 protein and NF-κB levels. HBO intervention significantly improved the BBB scores at 7 and 14 d post injury (P < 0.05).

CONCLUSIONS:

Hyperbaric oxygen reduced the expressions of HMGB1, TLR4, and NF-κB and reduced secondary SCI as measured using BBB scores.

KEYWORDS:

Hyperbaric oxygen; spinal cord injury; toll-like receptor 4

Brain Res. 2015 May 5;1606:68-76. doi: 10.1016/j.brainres.2015.01.029. Epub 2015 Feb 25.

The effects of hyperbaric oxygen on macrophage polarization after rat spinal cord injury.

Geng CK1, Cao HH2, Ying X3, Zhang HT4, Yu HL5.

Abstract

The immunoreactive responses are a two-edged sword after spinal cord injury (SCI). Macrophages are the predominant inflammatory cells responsible for this response. However, the mechanism underlying the effects of HBOT on the immunomodulation following SCI is unclear now. The present study was performed to examine the effects of hyperbaric oxygen therapy (HBOT) on macrophage polarization after the rat compressive injury of the spinal cord.

HBOT was associated with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IFN-ɣ levels. This was associated simultaneously with the levels of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased levels of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive).

These changes were associated with functional recovery in the HBOT-transplanted group, which correlated with preserved axons and increased myelin sparing. Our results suggested that HBOT after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, which may further promote the axonal extension and functional recovery.

 

Diving Hyperb Med. 2015 Sep;45(3):210.

Management of severe spinal cord injury following hyperbaric exposure

Mathew B1, Laden G2.

Author information

  • 1Consultant Neurosurgeon, Hull Trust Hospitals, Yorkshire, UK.

  • 2Clinical Hyperbaric Facility, Hull and East Riding Hospital, Hull, UK, E-mail: bruce.mathew@me.com.

Abstract

There is an increasing body of evidence that drainage of lumbar cerebrospinal fluid (CSF) improves functional neurological outcome after reperfusion injury to the spinal cord that occasionally follows aortic reconstructive surgery. This beneficial effect is considered owing to lowering of the CSF pressure thereby normalising spinal cord blood flow and reducing the 'secondary' cord injury caused by vascular congestion and cord swelling in the relatively confined spinal canal.

Whilst lacking definitive proof, there are convincing randomised controlled trials (RCTs), cohort data and systematic reviews supporting this intervention. The therapeutic window for lumbar CSF drainage requires further elucidation; however, it appears to be days rather than hours post insult. We contend that the same benefit is likely to be achieved following other primary spinal cord injuries that cause cord swelling and elicit the 'secondary' injury.

Traditionally the concept of CSF drainage has been considered more applicable to the brain as contained in a 'closed box' by lowering intracranial pressure (ICP) to improve cerebral perfusion pressure (CPP). The control of CPP is intended to limit 'secondary' brain injury and is a key concept of brain injury management. Using microdialysis in the spinal cords of trauma patients, it has been shown that intraspinal pressure (ISP) needs to be kept below 20 mmHg and spinal cord perfusion pressure (SCPP) above 70 mmHg to avoid biochemical evidence of secondary cord damage. Vasopressor have also been used in spinal cord injury to improve perfusion, however complications are common, typically cardiac in nature, and require very careful monitoring; the evidence supporting this approach is notably less convincing.

Decompression illness (DCI) of the spinal cord is treated with recompression, hyperbaric oxygen, various medications designed to reduce the inflammatory response and fluid administration to normalise blood pressure and haematocrit. These management protocols are based largely on anecdote and transferred evidence from conventional cord trauma, as the low numbers and sporadic nature of DCI in divers makes RCTs nigh on impossible. Unfortunately even with best management, some patients are left with significant neurological deficit. The 'iceberg phenomenon', occurs when patients with DCI of the cord make a good neurological recovery but actually have profound cord damage as revealed in one case some four years later at post mortem and another example in a diver who developed late functional deterioration due to loss of neuronal reserve. This clinical evidence, together with animal study data, support the notion that even a modest preservation of spinal cord axons is associated with significant improvement in neurological outcome. In the light of the positive level two evidence in the vascular literature that CSF drainage limits 'secondary' injury thereby improving neurological outcome, we propose that centres with appropriate clinical experience consider using lumbar CSF drainage to normalise SCPP, as an adjunct to the conventional treatment of severe spinal cord DCI. Divers with severe spinal cord DCI are generally in the most productive years of their lives and, given the potentially devastating impact of this condition, should be given the benefit of any possible adjuvant treatment that may serve to improve long-term outcome.

Asian Pac J Trop Med. 2015 Jun;8(6):468-73. doi: 10.1016/j.apjtm.2015.05.001. Epub 2015 Jun 25.

Effect of mesenchymal stem cells transplantation combining with hyperbaric oxygen therapy on rehabilitation of rat spinal cord injury

Geng CK1, Cao HH2, Ying X3, Yu HL4.

Author information

  • 1Department of Orthopedics, Yan'an Hospital of Kunming City, the Affiliated Hospital of Kunming Medical University, Kunming 650051, China; Department of Minimally Invasive Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.

  • 2Department of Hematology, Tumor Hospital of Yunnan Province & The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.

  • 3Department of Orthopedics, Yan'an Hospital of Kunming City, the Affiliated Hospital of Kunming Medical University, Kunming 650051, China.

  • 4Department of Minimally Invasive Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. Electronic address: 15877990976@163.com.

Abstract

OBJECTIVE:

To investigate the effect of BMSCs transplantation plus hyperbaric oxygen (HBO) on repair of rat SCI.

METHODS:

Seventy five male rats were divided randomly into five groups: sham, vehicle, BMSCs transplantation group, combination group, 15 rats in each group. Every week after the SCI onset, all animals were evaluated for behavior outcome by Basso-Beattle-Bresnahan (BBB) score and inclined plane test. Axon recovery was examined with focal spinal cord tissue by electron microscope at 6 weeks after the SCI onset. HE staining and BrdU staining were performed to examine the BMSCs and lesion post injury. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction.

RESULTS:

Results from the behavior tests from combination group were significant higher than rats which received only transplantation or HBO treatment. Results from histopathology showed favorable recovery from combination group than other treatment groups. The number of BrdU(+) in combination group were measureable more than transplantation group (P < 0.05). The greatest decrease in TNF-α, IL-1β, IL-6, IFN-α determined by Elisa assay in combination group were evident too.

CONCLUSIONS:

BMSCs transplantation can promote the functional recovery of rat hind limbs after SCI, and its combination with HBO has a synergistic effect.

Recent Pat Antiinfect Drug Discov. 2015 Mar 10. [Epub ahead of print]

Evaluation of Urinary Interleukin-8 Levels in Patients with Spinal Cord Injury

Rahimkhani M1, Mordadi A, Varmazyar S, Tavakoli A.

Author information

  • 1School of allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran. rrahimkhani@sina.tums.ac.ir.

Abstract

BACKGROUND:

Interleukins are a group of cytokines responsible for regulating inflammatory and infectious responses. Interleukin-8 plays an important role in chemotaxis and functioning of leukocytes and is locally produced in infected tissues; it is seen in abundance in the urine of individuals with Urinary Tract Infection.

MATERIALS & METHODS:

Midstream sterile urine sampling was performed in different patients admitted to the Spinal Cord Injury (SCI) research center. The samples were tested to determine the level of IL-8 through the ELISA method. The commercial kit used for this study was an R & D kit built in Germany.

RESULTS:

The mean level of IL-8 was 369.59pg/ml and 75.42pg/ml in male and female patients respectively. Among the 97 patients under study, 87 (89.7%) were IL-8 positive (>10 pg/ml) and 10 patients were IL-8 negative (<10 pg/ml). Among the 87 IL-8 positive subjects, 64 patients had no UTI symptoms, while 23 did.

CONCLUSION:

SCI patients should have their urinary IL-8 levels measured on a routine and periodic basis, irrespective of their SCI severity or the presence or absence of UTI symptoms. The timely and effective diagnosis & treatment of UTI can prevent the irreversible complications caused by frequent UTI and resistance to treatment in this group of patients.

Eur J Pain. 2014 Nov 20. doi: 10.1002/ejp.618. [Epub ahead of print]

Hyperbaric oxygenation treatment alleviates CCI-induced neuropathic pain and decreases spinal apoptosis

Hu Q1, Fang L, Li F, Thomas S, Yang Z.

Author information

  • 1Department of Anesthesiology, SUNY Upstate Medical University, Syracuse, USA.

Abstract

BACKGROUND:

Increased apoptotic changes in the spinal cord may be responsible for the development of chronic constriction injury (CCI)-induced neuropathic pain. We previously reported the beneficial effect of hyperbaric oxygen (HBO) in the treatment of CCI-induced neuropathic pain. In this study, we tested our hypotheses that HBO may achieve its beneficial effect by inhibiting CCI-induced proapoptosis gene expression and apoptosis in the spinal cord.

METHODS:

Male rats were randomized into: SHAM, CCI and CCI + HBO groups. Mechanical hyperalgesia was tested daily following surgery. CCI + HBO rats were treated with HBO for 1 h daily. At 3 days post-CCI, the expression of tumour necrosis factor (TNF)-α and caspase-3 genes was detected. At 7 days post-CCI, apoptotic cells in the spinal cord were detected.

RESULTS:

Three days post-CCI, mechanical allodynia had developed in the ipsilateral paw compared with SHAM animals. HBO significantly alleviated CCI-induced mechanical allodynia. In comparison with SHAM, CCI-induced neuropathic pain was associated with higher mRNA levels of TNF-α and caspase-3. HBO significantly decreased CCI-induced mRNA levels of TNF-α and caspase-3. CCI-induced neuropathic pain was also associated with more apoptotic cells in the spinal cord 7 days post-CCI. HBO significantly reduced CCI-induced apoptosis to the level of SHAM animals.

CONCLUSIONS:

Overly expressed proapoptosis genes, and subsequent increase in spinal apoptotic cells, seem to contribute to the development of CCI-induced neuropathic pain. The inhibitory role of HBO on spinal proapoptosis genes and apoptotic changes may contribute to its beneficial effect on CCI-induced neuropathic pain.

Int J Clin Exp Pathol. 2014 Apr 15;7(5):1911-9. eCollection 2014.

Protective effects of hyperbaric oxygen treatment against spinal cord injury in rats via toll-like receptor 2/nuclear factor-κB signaling

Tan J1, Zhang F2, Liang F3, Wang Y4, Li Z3, Yang J3, Liu X3.

Author information

  • 1Department of Hyperbaric Oxygen, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, 510120, Guangdong, China.

  • 2Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, 510120, Guangdong, China.

  • 3Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University Beijing, 100020, China.

  • 4Department of Hyperbaric Oxygen, Beijing Fu Xing Hospital, Capital Medical University Beijing, 100038, China.

Abstract

Spinal cord injury (SCI) is a serious medical problem with high mortality and disability rates. Hyperbaric oxygen (HBO) treatment is beneficial for neurological recovery after SCI, but the underlying mechanisms await characterization. This study examined whether HBO treatment following SCI in rats exerts a neuroprotective effect through activation of the toll-like receptor (TLR) 2/nuclear factor (NF)-κB signaling pathway. The SC of rats was injured via T10 laminectomy. Experimental animals (n=144) were divided into four groups: sham-operated (SH), SH+HBO, SCI, and SCI+HBO. Each group was subdivided into six subgroups (n=6 per group) that were examined at 12 h, and 1, 2, 3, 7, and 14 days post-injury. Functional recovery in the hind limb was evaluated using the Basso, Beattie, and Bresnahan (BBB) scoring system. The expression of TLR2 and NF-кB was assessed by real-time polymerase chain reaction and Western blotting, while interleukin-1 (IL)-1β and tumor necrosis factor (TNF)-α levels were measured by enzyme-linked immunosorbent assay. TLR2 and NF-кB levels and histological scores were higher in the SCI than in the SH and SH+HBO groups at various time points.

  • HBO treatment decreased TLR2 and NF-кB expression and histological scores as well as IL-1β and TNF-α levels compared to the SCI group at early post-injury stages. In addition, BBB scores were improved in the SCI+HBO relative to the SCI group at 7 and 14 days.

  • HBO treatment may mitigate secondary injury to the SC by inhibiting inflammatory responses induced by TLR2/NF-кB signaling, thereby promoting functional recovery and improving neurological outcome.