The SDF1-CXCR4 Axis Is Involved in the Hyperbaric Oxygen Therapy-Mediated Neuronal Cells Migration in Transient Brain Ischemic Rats.

Neurogenesis is a physiological response after cerebral ischemic injury to possibly repair the damaged neural network. Therefore, promoting neurogenesis is very important for functional recovery after cerebral ischemic injury. Our previous research indicated that hyperbaric oxygen therapy (HBOT) exerted neuroprotective effects, such as reducing cerebral infarction volume. The purposes of this study were to further explore the effects of HBOT on the neurogenesis and the expressions of cell migration factors, including the stromal cell-derived factor 1 (SDF1) and its target receptor, the CXC chemokine receptor 4 (CXCR4). Thirty-two Sprague-Dawley rats were divided into the control or HBO group after receiving transient middle cerebral artery occlusion (MCAO). HBOT began to intervene 24 h after MCAO under the pressure of 3 atmospheres for one hour per day for 21 days. Rats in the control group were placed in the same acrylic box without HBOT during the experiment. After the final intervention, half of the rats in each group were cardio-perfused with ice-cold saline followed by 4% paraformaldehyde under anesthesia. The brains were removed, dehydrated and cut into serial 20µm coronal sections for immunofluorescence staining to detect the markers of newborn cell (BrdU+), mature neuron cell (NeuN+), SDF1, and CXCR4. The affected motor cortex of the other half rats in each group was separated under anesthesia and used to detect the expressions of brain-derived neurotrophic factor (BDNF), SDF1, and CXCR4. Motor function was tested by a ladder-climbing test before and after the experiment. HBOT significantly enhanced neurogenesis in the penumbra area and promoted the expressions of SDF1 and CXCR4. The numbers of BrdU+/SDF1+, BrdU+/CXCR4+, and BrdU+/NeuN+ cells and BDNF concentrations in the penumbra were all significantly increased in the HBO group when compared with the control group. The motor functions were improved in both groups, but there was a significant difference between groups in the post-test. Our results indicated that HBOT for 21 days enhanced neurogenesis and promoted cell migration toward the penumbra area in transient brain ischemic rats. HBOT also increased BDNF expression, which might further promote the reconstructions of the impaired neural networks and restore motor function.

Effects of repetitive hyperbaric oxygen therapy on neuroprotection in middle cerebral artery occlusion rats.

Hyperbaric oxygen (HBO) has been suggested as a possible therapy for brain injury. However, the effects of HBO after transient brain ischemia are inconsistent and the underlying mechanisms are not fully known. The present study aimed to investigate the effects of repetitive HBO intervention in a transient middle cerebral artery occlusion (MCAO) animal model. Seventy-two Sprague-Dawley rats received MCAO and were randomly assigned to normal air control or HBO intervention groups. Each group was divided into 3 subgroups according to the intervention time period (7, 14, and 21 days). HBO was started 24 h post-MCAO for 1 h/day at 3.0 ATA with no-air breaks. After the final intervention, half of the rats in each subgroup were sacrificed and the right motor cortex was removed to examine levels of Akt phosphorylation and glutathione (GSH), as well as glutathione peroxidase (GPx) and reductase (GR) activity. The other half of the rats were used to examine infarct volume. At 24 h post-MCAO and the end of the final intervention, rats underwent tests to examine motor performance. We noted that 14- and 21-day HBO interventions significantly reduced infarct volume and increased Akt phosphorylation and GSH levels and GPx and GR activity. Motor performance was also significantly improved after 14- and 21-day interventions. No significant differences were observed between the controls and 7-day intervention groups. Repetitive HBO intervention starting 24 h post-MCAO and applied for at least 14 days, provided neuroprotective effects through modulating the cell survival pathway and antioxidative defense system.

Effects of hyperbaric oxygenation on oxidative stress in acute transient focal cerebral ischemic rats.

The aim of this study was to investigate the effects of hyperbaric oxygenation (HBO) after brain ischemia. Middle cerebral artery occlusion (MCAO) procedure was used to induce the brain ischemia. Rats were assigned to control or HBO group after brain ischemia. In order to examine the role of glutathione after HBO treatment, another group of brain ischemic rats were included to receive the glutathione synthesis inhibitor and HBO treatment. HBO was administered at a pressure of 3 atmospheres absolute for 1 h with 100% oxygen, starting at 3 h post brain ischemia in HBO groups. Animals in control group were placed in their home cage and exposed to normobaric room air. The infarct volume (IV), activation of astrocyte, and level of total glutathione and lipid peroxidation (LP) were assessed 24 h post-reperfusion. Significant reduction in IV was noted in HBO group when compared with control group. The activation of astrocyte was significantly increased in the right cerebral cortex and right striatum in the HBO group when compared with those of the control group. The glutathione level was higher with lower LP level in right cortex and right striatum after HBO as compared with those of the control. However, such effects of HBO treatment were markedly reduced by glutathione synthesis inhibitor administration. These results show that inhibiting glutathione synthesis dramatically reduces the effectiveness of HBO in acute transient focal cerebral ischemia.