This case report describes the use of acupuncture in the management of chronic central pain in a 51 year old man following severe traumatic brain injury and multiple injuries including rib fractures. The patient reported rapid and significant improvements in pain and mood during a course of acupuncture treatment. Chronic pain following traumatic brain injury is a significant problem. Chronic pain after rib fractures is also commonly reported. Acupuncture is widely used in the management of pain but its use has been reported rarely in the traumatic brain injury literature. This case report suggests that acupuncture may be a useful option to consider in these patients. Outcome was assessed formally using a 0-10 verbal numerical rating scale for pain, and the Hospital Anxiety and Depression Scale (HADS) for psychological status before and after the course of treatment. These scales are widely used in clinical practice as well as in research involving patients with traumatic brain injury, although they have not been validated in this population. The changes in this patient's outcome scores were not consistent with the benefits he reported. Treatment of this patient highlighted the difficulties of using standardised self rating scales for patients with cognitive impairment. The report also discusses the effects of acupuncture on this patient's mood.

This case report describes the use of acupuncture in the management of chronic central pain in a 51 year old man following severe traumatic brain injury and multiple injuries including rib fractures. The patient reported rapid and significant improvements in pain and mood during a course of acupuncture treatment. Chronic pain following traumatic brain injury is a significant problem. Chronic pain after rib fractures is also commonly reported. Acupuncture is widely used in the management of pain but its use has been reported rarely in the traumatic brain injury literature. This case report suggests that acupuncture may be a useful option to consider in these patients. Outcome was assessed formally using a 0-10 verbal numerical rating scale for pain, and the Hospital Anxiety and Depression Scale (HADS) for psychological status before and after the course of treatment. These scales are widely used in clinical practice as well as in research involving patients with traumatic brain injury, although they have not been validated in this population. The changes in this patient's outcome scores were not consistent with the benefits he reported. Treatment of this patient highlighted the difficulties of using standardised self rating scales for patients with cognitive impairment. The report also discusses the effects of acupuncture on this patient's mood.

Context:Traumatic brain injury (TBI) is an injury to the brain that occurs as a result of a direct impact, and affected persons are usually in a long-term coma. The evidence of the safety and effectiveness of acupuncture to treat coma is still not convincing.

Objective:The study intended to assess the effectiveness and safety of acupuncture for arousing a patient in a coma following TBI.

Design:Medline, Embase, CENTRAL, and 4 Chinese medical databases were searched from their inception to March 1, 2018, without language restrictions. The dataset included randomized controlled trials (RCTs) that examined acupuncture as a therapy for arousing patients in a coma after TBI. The literature was screened ;the data were extracted ;and the methodological quality of the included studies was assessed. Meta-analyses were performed on the included data.

Setting:This study was conducted at Tianjin University of Traditional Chinese Medicine (Tianjin City, China).

Participants:Participants in the selected RCTs were people of any age and either gender who were in a coma caused by TBI.

Interventions:The intervention group in the selected RCTs had received acupuncture for TBI, either as a sole therapy or combined with other treatments, and the control group had received placebo acupuncture, sham acupuncture, conventional treatments, or other treatments. The interventions included traditional acupuncture, electroacupuncture, ear acupuncture, and scalp acupuncture.

Outcome Measures:The research team measured the Glasgow Outcome Score (GOS), wake-promoting rates, as well as the Glasgow Coma Score (GCS).

Results:Of 884 potentially relevant trials, 24 RCTs met the inclusion criteria. The results of the meta-analysis suggested that the acupuncture group's coma state was significantly lessened after treatment compared with the control on GOS (RR, 1.95, 95% CI [1.64 to 2.31], P<.01; I² = 0%), wake-promoting rates (RR, 1.48, 95% CI [1.19 to 1.83], P<.01; I² = 52%), and GCS (MD, 1.78, 95% CI [1.10 to 2.45], P<.01; I² = 52%) .

Conclusion:The systematic review and meta-analysis has suggested that acupuncture can be an effective treatment for patients unconscious following TBI. However, the evidence was too weak for medical practitioners to routinely recommend acupuncture for clinical treatment; further large, rigorously designed studies are needed.

OBJECTIVE:To evaluate the immediate effect of acupuncture on cortico spinal tract (CST) activity in patients with chronic disorders of consciousness (DOC) after traumatic brain injury (TBI) by measuring motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS).

DESIGN:Changes in several variables in the acupuncture session were compared with those in the control session without acupuncture in the same patients.

SETTING:Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Gifu, Japan.

PATIENTS:Fourteen patients (mean age± standard deviation, 39 ± 17 years; 12 men) with chronic DOC (5 in a vegetative state and 9 in a minimally conscious state) following severe TBI.

INTERVENTION:Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes.

OUTCOME MEASURES:Main outcome measure was MEP amplitude. MEP amplitude, measured by using TMS on the primary motor cortex, was recorded from the abductor pollicis brevis muscle. MEP recordings were performed before acupuncture (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). As a control, the same procedure without acupuncture was performed on another day with the order randomized. MEP amplitude and latency were calculated. Evoked F-wave measurements were also performed to calculate maximum M-wave amplitude (Mmax), M-wave latency, and F-wave latency in the same muscle. Central motor conduction time (CMCT) and MEP/Mmax ratio were also calculated from the MEP and F-wave measurement data.

RESULTS:MEP amplitude and MEP/Mmax were increased significantly in the acupuncture session at phases 1 and 2 compared with the control session (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). CMCTs were reduced at phases 1 and 2 in the acupuncture session compared with the control session, and the change at phase 1 was statistically significant (P = 0.002).

CONCLUSIONS:Acupuncture treatment increased the CST activity of patients with chronic DOC after severe TBI.

Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18-65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT. Comparison was made using SPECT imaging on 29 matched Controls. Side effects (30 subjects) experienced due to the HBOT: reversible middle ear barotrauma (n = 6), transient deterioration in symptoms (n = 7), reversible bronchospasm (n = 1), and increased anxiety (n = 2; not related to confinement); unrelated to HBOT: ureterolithiasis (n = 1), chest pain (n = 2). Significant improvement (29 subjects) was seen in neurological exam, symptoms, intelligence quotient, memory, measures of attention, dominant hand motor speed and dexterity, quality of life, general anxiety, PTSD, depression (including reduction in suicidal ideation), and reduced psychoactive medication usage. At 6-month follow-up subjects reported further symptomatic improvement. Compared to Controls the subjects' SPECT was significantly abnormal, significantly improved after 1 and 40 treatments, and became statistically indistinguishable from Controls in 75% of abnormal areas. HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI PPCS with PTSD in all four outcome domains: clinical medicine, neuropsychology, psychology, and SPECT imaging. Veterans also experienced a significant reduction in suicidal ideation and reduction in psychoactive medication use.

We investigated the effects of hyperbaric oxygen treatment on the Nrf2 signaling pathway in secondary injury following traumatic brain injury, using a rat model. An improved Feeney freefall method was used to establish the rat traumatic brain injury model. Sixty rats were randomly divided into three groups: a sham surgery group, a traumatic brain injury group, and a group receiving hyperbaric oxygen treatment after traumatic brain injury. Neurological function scores were assessed at 12 and 24 h after injury. The expression levels of Nrf2, heme oxygenase 1 (HO-1), and quinine oxidoreductase 1 (NQO-1) in the cortex surrounding the brain lesion were detected by western blotting 24 h after the injury. Additionally, the TUNEL method was used to detect apoptosis of nerve cells 24 h after traumatic injury and Nissl staining was used to detect the number of whole neurons. Hyperbaric oxygen treatment significantly increased the expression of nuclear Nrf2 protein (P<0.05), HO-1, and NQO-1 in the brain tissues surrounding the lesion after a traumatic brain injury (P<0.05) and also significantly reduced the number of apoptotic and injured nerve cells. The neurological function scores also improved with hyperbaric oxygen treatment (P<0.05). Therefore, hyperbaric oxygen has a neuroprotective role in traumatic brain injury, which is mediated by up-regulation of the Nrf2 signaling pathway.

BACKGROUND:Traumatic brain injury (TBI) is accompanied by substantial accumulation of biomarkers of oxidative stress and depletion of antioxidants reserve which initiate chain reactions that damage brain cells. The present study investigated the role of ascorbic acid andα-tocopherol on the severity and management of TBI in rats.

MATERIALS AND METHODS:Wistar rats were subjected to closed head injury using an accelerated impact device. Rats were administered 45 mg/kg and 60 mg/kg body weight of ascorbic acid,α-tocopherol or a combination of the two vitamins for 2 weeks pre- and post injury. Blood and brain tissue homogenates were analyzed for vitamin C, vitamin E, malondialdehyde, superoxide dismutase, and creatine kinase activities.

RESULTS:The results indicated that TBI caused significant (P<0.05) decreased in vitamins C and E levels in the blood and brain tissue of TBI-untreated rats. The activities of superoxide dismutase in TBI rats were markedly reduced when compared with non traumatized control and showed a tendency to increased following supplementation with vitamins C and E. Supplementation of the vitamins significantly (P<0.05) reduced malondialdehyde in the treatment groups compared with the TBI-untreated group.

CONCLUSION:The study indicated that pre and post treatment with ascorbic acid andα-tocopherol reduced oxidative stress induced by brain injury and effectively reduced mortality rate in rats.

Growing evidence has demonstrated that the nucleotide‑binding oligomerization domain‑like receptor family pyrin domain containing 3 (NLRP‑3) inflammasome‑mediated inflammatory pathways have been involved in the secondary injury of traumatic brain injury (TBI). In the present study, the authors investigated the effects of hyperbaric oxygen (HBO) therapy on the NLRP‑3 inflammasome pathway following TBI. Following the evaluation of motor deficits and brain edema, the therapeutic effects of HBO on interleukin (IL)‑1β and IL‑18 expression were assessed, as well as NLRP‑3 inflammasome activation following TBI. HBO may improve motor score and reduce brain edema, accompanied with the reduction of IL‑1β and IL‑18 during the 7‑day observation period. Furthermore, HBO suppressed mRNA and protein expression of NLRP‑3‑inflammasome components, especially reducing NLRP‑3 expression in microglia. Thus, these results suggestedthat HBO alleviates the inflammatory response in experimental TBI via modulating microglial NLRP‑3‑inflammasome signaling.

OBJECTIVE:The aim of this study was to determine whether hyperbaric oxygen (HBO) therapy causes attenuation of traumatic brain injury (TBI)-induced depression-like behavior and its associated anti-neuroinflammatory effects after fluid percussion injury.

METHODS:Anesthetized male Sprague-Dawley rats were divided into three groups: sham operation + NBA (normobaric air: 21% O2 at 1 absolute atmosphere [ATA]), TBI + NBA, and TBI + HBO (100% O2 at 2.0 ATA). HBO was applied immediately for 60 min/day after TBI for 3 days. Depression-like behavior was tested by a forced-swimming test, motor function by an inclined plane test, and infarction volume by TTC staining on days 4, 8 and 15. Neuronal apoptosis (TUNEL assay), microglial (marker OX42) activation, and TNF-α expression in microglia in the hippocampus CA3 were measured by immunofluorescence methods.

RESULTS:Compared to the TBI controls, without significant changes in triphenyltetrazolium chloride (TTC) staining or in the motor function test, TBI-induced depression-like behavior was significantly attenuated by HBO therapy by day 15 after TBI. Simultaneously, TBI-induced neuronal apoptosis, microglial (marker OX42) activation, and TNF-α expression in the microglia in the hippocampus CA3 were significantly reduced by HBO.

CONCLUSIONS:Our results suggest that HBO treatment may ameliorate TBI-induced depression-like behavior in rats by attenuating neuroinflammation, representing one possible mechanism by which depression-like behavior recovery might occur. We also recommend HBO as a potential treatment for TBI-induced depression-like behavior if early intervention is possible.

Hyperbaric oxygen (HBO) therapy and neural stem cell (NSC) transplantation can improve traumatic brain injury (TBI) clinically. This study aimed to investigate the mechanism of HBO promoting NSC proliferation and neurological recovery after TBI. Twenty-four Sprague-Dawley rats were divided randomly into three groups: a sham group, a TBI group (constructed using Feeney's free-fall method), and an HBO-treated TBI group. Neurological function was evaluated by Neurological Severity Scores on days 1, 3, and 7, and we found that TBI-induced poor neurological function was improved by HBO. On day 7 after TBI, we observed that TBI promoted NSC proliferation, migration to the lesion area, and the levels of vascular endothelial growth factor (VEGF), VEGFR2, Raf-1, MEK1/2, and phospho-extracellular signal-regulated kinase (ERK) 1/2 protein, which were further boosted by HBO, from immunohistochemistry, immunofluorescence, and Western blot experiments. In vitro, cell injury was applied to NSCs isolated from neonatal Sprague-Dawley rats by the Cell Injury Controller II system. Moreover, data from the BrdU Kit and Western blot showed that in-vitro HBO significantly accelerated NSC proliferation and the levels of proteins related to cell cycle and the VEGF/ERK pathway after cell injury, which was suppressed by the VEGFR2 inhibitor. Taken together, this study indicated that HBO may promote NSC proliferation by activating VEGF/ERK signaling and play a crucial role in neuroprotection after TBI.

Background: Recent clinical studies in stroke and traumatic brain injury (TBI) victims suffering chronic neurological injury present evidence that hyperbaric oxygen therapy (HBOT) can induce neuroplasticity. Objective: To assess the neurotherapeutic effect of HBOT on prolonged post-concussion syndrome (PPCS) due to TBI, using brain microstructure imaging. Methods: Fifteen patients afflicted with PPCS were treated with 60 daily HBOT sessions. Imaging evaluation was performed using Dynamic Susceptibility Contrast-Enhanced (DSC) and Diffusion Tensor Imaging (DTI) MR sequences. Cognitive evaluation was performed by an objective computerized battery (NeuroTrax). Results: HBOT was initiated 6 months to 27 years (10.3± 3.2 years) from injury. After HBOT, DTI analysis showed significantly increased fractional anisotropy values and decreased mean diffusivity in both white and gray matter structures. In addition, the cerebral blood flow and volume were increased significantly. Clinically, HBOT induced significantimprovement in the memory, executive functions, information processing speed and global cognitive scores. Conclusions: The mechanisms by which HBOT induces brain neuroplasticity can be demonstrated by highly sensitive MRI techniques of DSC and DTI. HBOT can induce cerebral angiogenesis and improve both white and gray microstructures indicating regeneration of nerve fibers. The micro structural changes correlate with the neurocognitive improvements.

Traumatic brain injury (TBI) is a serious public health problem in the United States. Survivors of TBI are often left with significant cognitive, behavioral, and communicative disabilities. So far there is no effective treatment/intervention in the daily clinical practice for TBI patients. The protective effects of hyperbaric oxygen therapy (HBOT) have been proved in stroke; however, its efficiency in TBI remains controversial. In this review, we will summarize the results of HBOT in experimental and clinical TBI, elaborate the mechanisms, and bring out our current understanding and opinions for future studies.

There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO2) in the context of an impending National Institute of Neurologic Disorders and Stroke (NINDS)-funded, multicenter, randomized, adaptive Phase II clinical trial - the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (8 clinical and 22 pre-clinical) that administered HBO2 within 30 days of a TBI were identified from PubMed searches. The pre-clinical studies consistently reported positive treatment effects across a variety of outcome measures with almost no safety concerns, thus providing strong proof-of-concept evidence for treating severe TBI in the acute setting. Of the 8 clinical studies reviewed, 4 were based on the senior author's (GR) investigation of HBO2 as a treatment for acute severe TBI. These studies provided evidence that HBO2 significantly improves physiologic measures without causing cerebral or pulmonary toxicity and can potentially improve clinical outcome. These results were consistent across the other 4 reviewed clinical studies, thus providing preliminary clinical data supporting the HOBIT trial. This comprehensive review demonstrates that HBO2 has the potential to be the first significant treatment in the acute phase of severe TBI.

Traumatic brain injury (TBI) may cause persistent cognitive dysfunction. A pilot clinical study was performed to determine if hyperbaric oxygen (HBO₂) treatment improves cognitive performance. It was hypothesized that stem cells, mobilized by HBO₂ treatment, are recruited to repair damaged neuronal tissue. This hypothesis was tested by measuring the relative abundance of stem cells in peripheral blood and cognitive performance during this clinical trial. The subject population consisted of 28 subjects with persistent cognitive impairment caused by mild to moderate TBI suffered during military deployment to Iraq or Afghanistan. Fluorescence-activated cell sorting (FACS) analysis was performed for stem cell markers in peripheral blood and correlated with variables resulting from standard tests of cognitive performance and post-traumatic stress disorder: ImPACT, BrainCheckers and PCL-M test results. HBO₂ treatment correlated with stem cell mobilization as well as increased cognitive performance. Together these results support thehypothesis that stem cell mobilization may be required for cognitive improvement in this population.

Repetitive mild traumatic brain injury (rmTBI) is an important medical concern for adolescent athletes that can lead to long-term disabilities. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the increased brain vulnerability to rmTBI and the effect of hyperbaric oxygen treatment using a juvenile rat model of rmTBI. Two episodes of mild cortical controlled impact (3 days apart) were induced in juvenile rats. Hyperbaric oxygen (HBO) was applied 1 hour/day× 3 days at 2 atmosphere absolute consecutively, starting at 1 day after initial mild traumatic brain injury (mTBI). Neuropathology was assessed by multi-modal magnetic resonance imaging (MRI) and tissue immunohistochemistry. After repetitive mTBI, there were increases in T2-weighted imaging-defined cortical lesions and susceptibility weighted imaging-defined cortical microhemorrhages, correlated with brain tissue gliosis at the site of impact. HBO treatment significantly decreased the MRI-identified abnormalities and tissue histopathology. Our findings suggest that HBO treatment improves thecumulative tissue damage in juvenile brain following rmTBI. Such therapy regimens could be considered in adolescent athletes at the risk of repeated concussions exposures.

This case report illustrates the improvement of an acupuncture-treated patient who incurred a severe traumatic brain injury (TBI) from a snowboarding accident. Over 4 years, the patient progressed from initially not being able to walk, having difficulty with speech, and suffering from poor eyesight to where he has now regained significant motor function, speech, and vision and has returned to snowboarding. A core acupuncture protocol plus specific points added to address the patient's ongoing concerns was used. This case adds to the medical literature by demonstrating the potential role of acupuncture in TBI treatment.

This case report illustrates the improvement of an acupuncture-treated patient who incurred a severe traumatic brain injury (TBI) from a snowboarding accident. Over 4 years, the patient progressed from initially not being able to walk, having difficulty with speech, and suffering from poor eyesight to where he has now regained significant motor function, speech, and vision and has returned to snowboarding. A core acupuncture protocol plus specific points added to address the patient's ongoing concerns was used. This case adds to the medical literature by demonstrating the potential role of acupuncture in TBI treatment.

Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.

This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, anti-oxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered.

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.