Hyperbaric Oxygen Therapy (HBOT) has
been used in experimental set-ups and case studies as an effected method for
the treatment of traumatic brain injury (TBI), ischemic and hemorrhagic stroke,
Alzheimer’s disease (AD), Diabetes mellitus (Yang et al., 2017;
Baratz-Goldstein et al., 2017; Harch et al., 2017; Zhai et al., 2016; Shapira
et al., 2018; Estrada et al., 2008). HBOT is the exposure to pure (100%) oxygen
which is pressurised to over 1 atm in a closed chamber (Baratz-Goldstein et al.,
2017; Shapira et al., 2018). The therapeutic time window for HBO treatment in
stroke has been suggested as 3 hours after the stroke. For a higher efficacy,
HBOT could be applied in an earlier time window (Zhai et al., 2016).
Combination therapies of HBOT and
stem cell transplantation/infusion have been reported by some groups on the improvement
compared to the monotherapy methods in spinal cord injury (SCI) (bone marrow
stem cells-transplantation), TBI (NSC transplantation) and Diabetes mellitus
(bone marrow stem cells-infusion) (Dekmak et al., 2018; Geng et al., 2015; Zádori et
al., 2011; Estrada et al., 2008).
In TBI model of NMRI mice, NSCs have
found to survive better in hypoxic areas of the brain whereas not capable to
differentiate. The cells in the damaged brain areas can gain its
differentiation following to oxygenation by HBOT. The animals have been subjected
to cold lesion which is the attachment of a copper rot at -60 ?C to the dura
matter for 30 s following to the craniotomy (day 0= D0). 7 days after the
freeze-lesion, 0.5–1×105 GFP-4C mouse NSCs have been transplanted into
the peri-lesion areas. Further they were subjected to 90 min hyperbaric
oxygen 2.5 ATA pressure
for 7 days after the implantation.
Implanted NSCs could not be detected in the intact forebrain after 1 month of
transplantation in both HBOT and without treatment groups. On the other
hand, few cells were detected in lesioned cortices in all time points (3 weeks, 7 weeks post-implantation) (Zádori et
Lee et al have investigated the
migration of bone marrow stem cells (BMSCs) after HBOT in middle cerebral
artery occlusion (MCAO). The rats were subjected to pure oxygen at 253 kPa (2.5
atm) for 90 mins. CD34-DAPI double
staining results have revealed that BMSC population in ischemic tissue after 3
weeks of HBOT was significantly higher than MCAO without HBOT and sham group,
but no significance compared to 2 days treatment group. NeuN and BrdU double
staining approach has shown that 3 weeks of HBOT has led to significant amount
of new neuron generation compared to all groups. Also increased level of
neurotrophic factors (BDNF: brain-derived neurotrophic factor and GDNF:
glial-derived neurotrophic factor) have been found throughout the time schedule
of the study (3 weeks) (Lee et al., 2013).
Activation of endogenous
neurogenesis in subventricular zone (SVZ) following to the HBO treatment in
ischemic and TBI rat models has been observed by different groups (Feng et al.,
2013; Yang et al., 2017). Neural stem cells (NSCs) in SVZ have shown increased
proliferation rate in neonatal rats with hypoxic-ischemic brain damage after 7
days of treatment
at 3 atm for 1 hour. The neuropathological conditions have found be
declined in HBO-treated group (Feng et al.,2013).
In Sprague Dawley rat model,
Hyperbaric Oxygen Therapy (HBOT) has been applied 3 hours after the
introduction of experimental traumatic brain injury (TBI). The rats treated
with 2 atm of constant pressure for 1 hour once a day for 7 days. Regular
neurological function evaluations have revealed that the animals with TBI
showed improvement after HBOT. The lesion size has decreased significantly in
the group treated with HBOT after TBI when compared to the TBI and sham groups.
The migrating and proliferating BrdU- and Nestin-positive neural stem cell
(NSC) population was detected in hippocampal dentate gyrus (DG) region. As a
proof of concept, in order to show the effect of VEGF on neural stem cell
proliferation, the isolated neonatal NSCs were exposed to VEGF inhibitor. In
the presence of VEGFR2-inhibitor (BIBF) the Ki-67, Nestin and cyclin D1 levels
have decreased in cell injury model with HBOT when compared to the cells
without injury and were treated by HBO (Yang et al., 2017).
In animal stroke and Alzheimer’s
disease models, it has been reported that HBOT has ameliorated the neurological
dysfunctions in long term applications (Zhai et al., 2016; Shapira et al., 2018).
Further, it has been shown that HBOT declines the neuroinflammation by reducing
astrogliosis and number of microglia
as well as secretion of proinflammatory cytokines (Shapira et al., 2018).
1 hour after the introduction of
TBI, Sprague Dawley rats were treated with HBO at 2.2 atm for 3 weeks. Throughout
the somatosensory-evoked potentials (SSEP) analysis, central conduction time
(CCT) has increased in HBO-treated and untreated TBI groups. 3 weeks after the
treatment CC time has declined significantly in HBO-treated group compared to
untreated group in ipsilateral hemisphere. On the other hand, contralateral
hemisphere data have shown spontaneous recovery and CC times has decreased in
both groups (Kraitsy et al., 2014).
Following to the closed head
model TBI introduction, HBOT was administered for 4 days. Two different time
points were chosen for the HBOT administration: 3 hours and 7 days post-TBI.
Moderate TBI (mTBI) group has shown increased neuronal loss and increased
reactive astrocytes whereas HBO treated group has not shown these results and
had similar results to the sham group (Baratz-Goldstein et al., 2017).
Different groups have reported clinical applications of HBOT
on TBI as well as post-concussion syndrome (PPCS) after TBI (Tal et al., 2017;
Harch et al., 2017; Boussi-Gross et al., 2013).
Improvement of neurocognitive
scores (memory, information processing speed, attention, executive function)
has been observed after HBO treatment followed for 40 daily sessions at 1.5 atm
for 60 min, 5 days a week (Boussi-Gross et al., 2013). Similar results have
been obtained except from in case of attention by Tal et al. after 60 daily
sessions of HBOT at 2 atm for 90 min. On the other hand, Diffusion Tensor
Imaging (DTI) analysis has revealed changes in mean diffusivity (MD) and
fractional anisotropy (FA). Decrease in MD and increase in FA have been
detected which in turn correlates with increase in fiber tracts in white
matter. Also, significant increase in cerebral blood flow (CBF) and cerebral
blood volume (CBV) in frontal white matter has been found. In the light of
these data, it has been concluded that HBOT increased microstructure recovery
and induced in cerebral angiogenesis (Tal et al.,2017).