Department of Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca, Romania; "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania.
International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
Int Rev Neurobiol. 2019;146:83-102. doi: 10.1016/bs.irn.2019.06.007. Epub 2019 Jul 18.
There is a growing trend of hypertension among military and civilian populations due to lifetime stressful situations. If hypertension is uncontrolled it leads to development of diabetes and serious neurological complications. Most of the World populations live in temperate zone across the World. Thus, a possibility exists that these hypertensive and diabetic people may have external heat as potential risk factors for brain damage. We have seen brain edema and brain damage following exposure to heat stress at 38°C for 4h. A possibility exists that heat exposure in diabetic-hypertensive (DBHY) cases exacerbates exacerbation of brain pathology and edema formation. This hypothesis is examined in a rat model. The role of nitric oxide (NO) in exacerbation of HS-induced brain pathology was also evaluated using nitric oxide synthase (NOS) immunoreactivity. Hypertensive rats (produced by two-kidney one clip (2K1C) method) were made diabetic with streptozotocine (50mg/kg, i.p./day for 3days) treatment. After 6weeks, DBHY rats show 20-30mM/L Blood Glucose and hypertension (180-200mmHg). Subjection of these rats to 4h HS resulted in six- to eightfold higher BBB breakdown, brain edema formation and brain pathology. At this time, neuronal or inducible NOS expression was four- to sixfold higher in DBHY rats compared to controls. Interestingly, iNOS expression was higher than nNOS in DBHY rats. Cerebrolysin in high doses (10-mL/kg, i.v. instead of 5-mL/kg) induced significant neuroprotection and downregulation of nNOS and iNOS in DBHY animals whereas normal animals need only 5-mL/kg doses for this purpose. Our observations demonstrate that co-morbidly factors exacerbate brain damage in HS through NOS expression and require double dose of cerebrolysin for neuroprotection as compared to normal rats, not reported earlier.
由于终身紧张的情况，军人和平民群体中的高血压发病率呈上升趋势。如果高血压得不到控制，它会导致糖尿病和严重的神经并发症的发展。世界上大多数人口生活在世界各地的温带地区。因此，存在这样一种可能性，即这些高血压和糖尿病患者可能会有外部热作为潜在的脑损伤危险因素。我们已经看到，在 38°C 下暴露于热应激 4 小时后，会出现脑水肿和脑损伤。在糖尿病-高血压（DBHY）病例中，热暴露可能会加剧脑病理和水肿形成的恶化。在大鼠模型中检验了这一假说。还使用一氧化氮合酶（NOS）免疫反应性评估了一氧化氮（NO）在加剧 HS 诱导的脑病理中的作用。通过两肾一夹（2K1C）方法产生的高血压大鼠用链脲佐菌素（50mg/kg，腹腔内注射/天，连续 3 天）制成糖尿病。6 周后，DBHY 大鼠的血糖为 20-30mM/L，且伴有高血压（180-200mmHg）。将这些大鼠置于 4 小时的 HS 下，导致 BBB 通透性增加了六至八倍，脑水肿形成和脑病理增加。此时，与对照组相比，DBHY 大鼠的神经元型或诱导型 NOS 表达增加了四至六倍。有趣的是，在 DBHY 大鼠中 iNOS 表达高于 nNOS。大剂量脑活素（10-mL/kg，静脉注射，而不是 5-mL/kg）可诱导 DBHY 动物的显著神经保护作用，并下调 nNOS 和 iNOS，而正常动物仅需 5-mL/kg 剂量即可达到此目的。我们的观察结果表明，共病因素通过 NOS 表达使 HS 中的脑损伤恶化，并需要双倍剂量的脑活素来实现神经保护，这在以前的报道中尚未提及。
