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C. Heng Chih1, Y. Yea Ru2, W. Ray Yau2
1Asia University, Department of Physical Therapy, Taichung, Taiwan, 2National Yang-Ming University, Department of Physical Therapy and Assistive Technology, Taipei, Taiwan
Background: Neurogenesis after brain ischemia has been suggested to be one of neural plasticity. The neural progenitor cells in the subventricular zone are increased after brain ischemia and has been demonstrated to migrate toward the penumbra area of affected cerebral cortex. Hyperbaric oxygen therapy (HBO) has the neuroprotective effects, such as decreasing the inflammation, blood-brain barrier rupture, and promoting neurogenesis. Our previous study indicates that sustained HBO decreases infarct volume and improves motor function with increase antioxidative effects. However, whether sustained HBO has effects on neural cell migration and/or differentiation are not well known.
Purpose: In this study, we aimed to investigate the effects of 21 days of HBO therapy on the neuronal cells expression in the penumbra area of affected cortex after transient middle cerebral artery occlusion (MCAO).
Methods: 32 SD rats are received transient MCAO, and then divided into control or HBO groups (N=16 each group). The HBO therapy was started from 24h post-MCAO, 1h per time, once per day for 21 days. The motor tests were done at 24h post-MCAO and after the finial intervention. The affected motor cortex of half of rats in each group were isolated and used to examine the expression of brain derived neurotrophic factor (BDNF). The brain of the other half of the rats in each group was perfused with 4% paraformaldehyde, and the motor area was cut into 20 μm sections. The brain sections were stained by using immunofluorescence to determine the expression of new born neuronal cells (BrdU+/NeuN+) and the migration biomarkers, including SDF1 and CXCR4.
Results: The results showed that 21 days HBO therapy enhanced the expressions of new born neuronal cells (BrdU+/NeuN+) in the penumbra area of affected motor cortex when compared with the control group (P<0.01). The new born neuronal cells were also co-stained with SDF1 and CXCR4 biomarkers in HBO groups, and showed significantly increased when compared with control group (P<0.01 in NeuN+/SDF1+ cells and NeuN+/CXCR4+ cells). The expression of BDNF in the affected motor cortex was also significantly increased in rats with HBO therapy.
Conclusion(s): Our results indicated that sustained HBO therapy could promote neurogenesis in the penumbra area of affected motor cortex after transient MCAO. Sustained HBO therapy also enhanced the neural progenitor cells to migrate toward the penumbra area of affected motor cortex and to differentiate into neuronal cells. The BDNF signaling might also participate in the neural plasticity after HBO therapy.
Implications: HBO therapy has been used in brain stroke patients during early stage after stroke and showed positive effects in the reduce of cranial pressure. This study further indicated that sustained HBO therapy could promote neural progenitor cells migration and differentiation into mature neuronal cells. These results provided an basic medical evidence for further clinical trials.
Funding, acknowledgements: The present study was supported by the Ministry of Science and Technology, Republic of China (R.O.C.) (MOST 103-2314-B-010-MY3 & 109-2314-B-468-005)
Keywords: Hyperbaric oxygen therapy, Neurogenesis, Brain ischemia
Topic: Neurology: stroke
Did this work require ethics approval? Yes
Institution: National Yang-Ming University, Taipei, Republic of China (R.O.C.)
Committee: Institutional Animal Care and Use Committee of National Yang-Ming University
Ethics number: IACUC-1021256
All authors, affiliations and abstracts have been published as submitted.
