Prophylactic treatment of hyperbaric oxygen treatment mitigates inflammatory response via mitochondria transfer

Abstract

Summary Aims Hyperbaric oxygen therapy (HBOT) has been widely used as postinjury treatment; however, we investigate its ability to mitigate potential damage as a preconditioning option. Here, we tested the hypothesis that HBOT preconditioning mitigates cell death in primary rat neuronal cells (PRNCs) through the transfer of mitochondria from astrocytes. Methods Primary rat neuronal cells were subjected to a 90‐minute HBOT treatment at 2.5 absolute atmospheres prior to either tumor necrosis factor‐alpha (TNF‐alpha) or lipopolysaccharide (LPS) injury to simulate the inflammation‐plagued secondary cell death associated with stroke and traumatic brain injury (TBI). After incubation with TNF‐alpha or LPS, the cell viability of each group was examined. Results There was a significant increase of cell viability accompanied by mitochondrial transfer in the injury groups that received HBOT preconditioning compared to the injury alone groups (44 ± 5.2 vs 68 ± 4.48, n = 20, P < 0.05). The transfer of mitochondria directly after HBOT treatment was visualized by capturing images in 5‐minute intervals, which revealed that the robust transfer of mitochondria begins soon after HBOT and persisted throughout the treatment. Conclusion This study shows that HBOT preconditioning stands as a robust prophylactic treatment for sequestration of inflammation inherent in stroke and TBI, possibly facilitating the transfer of resilient mitochondria from astrocytes to inflammation‐susceptible neuronal cells in mitigating cell death.

Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination

“…However, the results of some studies have suggested that extracellular mitochondria play unfavorable roles. Mitochondria from traumatized brain tissues were able to stimulate platelets and promote their procoagulant activity, contributing to TBI-induced coagulopathy and in ammation [76]. Furthermore, in our present study, we also surprisingly observed that the protective effects of isolated mitochondria were oxygen-dependent, where the treatment of isolated mitochondria could cause detrimental effects under hypoxic conditions and promote protective effects in a normal oxygen environment.…”

Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients – a retrospective analysis

“…Oxygenation improves energy metabolism in the border zones of focal cerebral ischemia represented by significant reduction of areas with tissue acidosis and areas with ATP depletion (Sun, Marti, & Veltkamp, 2008;Sun, Strelow, Mies, & Veltkamp, 2011).HBOT can also decrease the post ischemic inflammatory response by reducing blood-brain-barrier damage (Veltkamp et al, 2005), inflammatory cytokines release (Yu, Xue, Liang, Zhang, & Zhang, 2015) and suppresses the aggravated response of astrocytes and microgliosis (Gunther et al, 2005). Recently, it was shown HBOT mitigates the inflammatory response of the neuronal cells through the transfer of mitochondria from astrocytes (Lippert & Borlongan, 2019). HBOT reduces apoptosis which enables to preserve more brain tissues and promote neurologic functional recovery (Yin et al, 2003).…”

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

“…Stroke and TBI, two principal forms of ABI, pose a significant health and economic burden globally, and limited treatment options necessitate a novel therapeutic strategy to attenuate disease progression. [88][89][90][91] Primary cell death directly results from stroke or TBI, and the extent of this, brain damage is categorized as either focal or diffuse. Along with the influence of patient age, central and peripheral sources of immune cells prominently contribute to secondary neurodegeneration during both the acute and chronic phases following stroke and TBI.…”