Clinical Trial – Effects of Repetitive Hyperbaric Oxygen Therapy in Patients With Acute Ischaemic Stroke

Background and Rationale:

Cerebrovascular disease is always ranked at the top causes of death and most of hospitalized
acute stroke patients have ischemic stroke [1].

Although the mortality rate of acute ischemic stroke is less than that of hemorrhagic stroke
[1], it still results in patient disabilities and complications that often lead to
significant costs to individuals, families, and society.

Traditional treatment for acute ischemic stroke includes thrombolytic therapy by injecting
tissue plasminogen activator (t-PA) within three hours after onset of symptoms [2],
antiplatelets and/or anticoagulant agents administered within the first 48 hours. Clinically,
the narrow time window of thrombolytic therapy and coexisting contraindications limit the use
of t-PA [2]. Thus, searching for an effective supplemental treatment for acute ischemic
stroke is imperative.

Hyperbaric oxygen therapy (HBOT) is valuable in treating acute carbon monoxide poisoning
[3,4], air or gas embolism [5], facilitating wound healing [6] and has been used as an
adjuvant treatment for many neurological disorders that need further study as concussion [7]
, stroke [8,9], cerebral palsy [ 10],traumatic brain injury [ 11], cerebral air embolism
[12], Autism [13] and multiple sclerosis [14].

Indications of hyperbaric oxygen therapy recommended by undersea and hyperbaric medical
society (UHMS) [15] are 1.air or gas embolism [5], 2.carbon monoxide poisoning [3,4],
3.clostridial myositis and myonecrosis [16], 4.crush injury, compartment syndrome and other
acute traumatic ischemias [17], 5.decompression sickness [18], 6.arterial insufficiencies
[19], 7.severe anemia [20], 8.intracranial abscess [21], 9.necrotizing soft tissue infections
[22],10. refractory osteomyelitis [23], 11.delayed radiation injury [24], 12.compromised
grafts and flaps [25], 13.acute thermal burn injury [26] and 14.idiopathic sudden
sensorineural hearing loss [27].

Known mechanisms of HBOT-induced neuroprotection include enhancing neuronal viability via
increased tissue oxygen delivery to the area of diminished blood flow, reducing brain edema,
and improving metabolism after ischemia [28,29]. Furthermore, a recent study performed on a
rat suggested that upregulation of the expression of glial derived neurotrophic factor (GDNF)
and nerve growth factor (NGF) might underlie the effect of HBOT [30].

The effectiveness of use of Hyperbaric oxygen therapy in human ischemic stroke is still
controversial that need further evaluation.

Clinical Trial – Effects of Hyperbaric Oxygen Therapy in Autistic Children: A Pilot Study

Autism is a neurodevelopmental disorder that currently affects as many as 1 out of 166
children in the United States. Autism is considered by many to be a permanent condition with
little hope for improvement. Treatment for autism is centered on special schooling and
behavioral therapy; medical science currently has little to offer.

Recent research has discovered that some autistic individuals have decreased blood flow to
the brain, evidence of inflammation in the brain, and increased markers of oxidative stress.
Multiple independent single photon emission computed tomography (SPECT) and positron emission
tomography (PET) research studies have revealed hypoperfusion to several areas of the
autistic brain, most notably the temporal regions and areas specifically related to language
comprehension and auditory processing. Several studies show that diminished blood flow to
these areas correlates with many of the clinical features associated with autism including
repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication,
sensory perception, and social interaction. Hyperbaric oxygen therapy (HBOT) has been used
with clinical success in several cerebral hypoperfusion syndromes including cerebral palsy,
fetal alcohol syndrome, closed head injury, and stroke. HBOT can compensate for decreased
blood flow by increasing the oxygen content of plasma and body tissues and can even normalize
oxygen levels in ischemic tissue. In addition, animal studies have shown that HBOT has potent
anti-inflammatory effects and reduces oxidative stress. Furthermore, recent evidence
demonstrates that HBOT mobilizes stem cells from human bone marrow which may aid recovery in
neurodegenerative diseases. Based upon these findings, it is hypothesized that HBOT will
improve symptoms in autistic individuals.

The purpose of this study is to determine if HBOT improves clinical outcomes in children with
autism. The study will also determine if HBOT changes markers of inflammation and oxidative
stress in autistic children.