Long Course Hyperbaric Oxygen Stimulates Neurogenesis and Attenuates Inflammation after Ischemic Stroke

Abstract

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats

“…Ischemic stroke is induced by cerebral artery occlusion, which can cause regional cerebral flow reduction or interruption (1). The brain is sensitive to ischemia, the effect of which may be exacerbated by the reperfusion.…”

Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: A Review

“…Opposite results were also found in some previous experiments for several hours after ischemia-reperfusion by using HBO therapy [50,51] . Recently, a new study [52] has testified that HBO might attenuate inflammation in transient MCAO rats with a long-course schedule (3 weeks or 2 days after MCAO, repeated for 3 weeks). This point has also been reflected in the HBO therapy of traumatic brain injury [53] .…”

“…Simultaneously, studies have shown that the positive effects still exist in brain damage [75] and spinal cord injury [76] . Long-course and repeated HBO therapy for cerebral ischemia can also generate similar outcomes [52,77] .…”

“…Previous studies proved that bone marrow stem cells have the ability to secrete GDNF, BDNF and NGF, and play a role in anti-inflammatory, anti-apoptotic, as well as host immune response [79,80] . Lee et al [52] have shown that HBO therapy is more likely to promote the mobilization and migration of bone marrow stem cells in MCAO rats via CD34-DAPI double staining.…”

“…Mu et al [102] further explain that delayed daily HBO therapy stimulate cell proliferation and generate neuroprotective effects via stabilizing the cAMP responsive element binding protein pathway. Based on the knowledge from some preclinical and clinical studies, HBO therapy has recently been shown to be effective when started 2-5 days after ischemic stroke onset [52,77] , or even in the chronic phase [20] . These studies provide references, as well as directions, for further studies of the mechanisms and clinical applications of HBO treatment.…”