Hari S. Sharma, Lianyuan Feng, Jose V. Lafuente, Dafin F. Muresanu, Zhenrong R. Tian, Ranjana Patnaik and Aruna Sharma Pages 386 - 399 ( 14 )
We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x106) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.
Blood-brain barrier, brain edema, brain pathology, diabetes, mesenchymal stem cells, neuronal injury, neuroprotection, nanowiring, streptozotocin, TiO2 nanowires, whole body hyperthermia.
Laboratory of Cerebrovascular Research, Dept. of Surgical Sciences, Anesthesiology & Intensive Care medicine, University Hospital, Uppsala University, Frodingsgatan 12:28, SE-75185 Uppsala, Sweden.