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

Abstract

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.

The Role of Hyperbaric Oxygen Therapy in the Treatment of Surgical Site Infections: A Narrative Review

“…Several experimental and clinical studies also showed a beneficial effect from HBOT in brain/cerebral injuries [41][42][43]. Animal studies have shown the inhibitory effect of HBOT on inflammation and apoptosis after cerebral ischemia [41,44]. Furthermore, these studies have shown that HBOT is associated with reduced blood-brain barrier breakdown, reduced cerebral edema, improved cerebral oxygenation, decreased intracranial pressure, reduced oxidative burden, reduced metabolic derangement, and increased neural regeneration [41,42,45].…”

Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke

“…Additionally, HBOT increases the expression of BDNF, further facilitating the reconstruction of impaired neural networks and potentially contributing to the restoration of motor function. The involvement of the ROS/HIF-1α/β-catenin pathway in these processes has also been suggested [97]. Functional electrical stimulation has been reported to promote neurogenesis in the brains of acute ischemic stroke rats.…”

Reactive Oxygen Species (ROS)-Mediated Antibacterial Oxidative Therapies: Available Methods to Generate ROS and a Novel Option Proposal

“…Currently, HBOT is considered both alone and in combination with different antibacterial treatment a relevant option for solving several cute or chronic diseases [249,251,257,258]. Although animal studies have shown the inhibitory effect of HBOT on inflammation and apoptosis after cerebral ischemia [259,260], clinical trials on humans have not shown any significant benefit. Anyway, it has been indicated that HBOT can improve some neuropsychological and inflammatory outcomes, especially in stroke patients, within the first few hours [261,262].…”