Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model

Elham H.A. Ali; Omar A. Ahmed-Farid; Amany A. E. Osman

doi:10.4103/1673-5374.221155

摘要：Sodium nitrite (NaNO2) is an inorganic salt used broadly in chemical industry. NaNO2is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against NaNO2 induced hypoxic brain injury. Rats were divided into control group (treated for 3 or 6 weeks), hypoxic (HP) group (subcutaneous injection of 35 mg/kg NaNO2for 3 weeks to induce hypoxic brain injury), HP recovery groups N-2wR and N-3wR (treated with the same dose of NaNO2for 2 and 3 weeks respectively, followed by 4-week or 3-week self-recovery respectively), and MSCs treated groups N-2wSC and N-3wSC (treated with the same dose of NaNO2for 2 and 3 weeks respectively, followed by one injection of 2 × 106MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of NaNO2 for 1 week in combination with 3 week self-recovery). The levels of neurotransmitters (norepinephrine, dopamine, serotonin), energy substances (adenosine monophosphate, adenosine diphosphate, adenosine triphosphate), and oxidative stress markers (malondialdehyde, nitric oxide, 8-hydroxy-2'-deoxyguanosine, glutathione reduced form, and oxidized glutathione) in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, patho-logical change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2'-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine tri-phosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine monophosphate/adenosine triphosphate ratio were significantly increased in the MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit neu-roprotective effects against NaNO2-induced hypoxic brain injury through exerting anti-oxidative effects and providing energy to the brain.