Sandu Raluca Elena, Uzoni Adriana, Ciobanu Ovidiu, Moldovan Mihai, Anghel Andrei, Radu Eugen, Coogan Andrew N, Popa-Wagner Aurel
University of Medicine and Pharmacy, Craiova, Romania.
Molecular Psychiatry, Department of Psychiatry, University of Medicine Rostock, Rostock, Germany.
Restor Neurol Neurosci. 2016 Feb 24;34(3):401-14. doi: 10.3233/RNN-150600.
In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. In animal studies of focal ischemia, short-term hypothermia often reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole body temperature. Previously, we reported that post-stroke exposure to hydrogen sulfide (H2S) effectively lowers whole body temperature and confers neuroprotection in aged animals.
In the present study using behavioral tests, MRI, telemetrical EEG, BP and temperature recordings, RT-PCR and immunofluorescence, we assessed infarct size, vascular density, neurogenesis and as well as the expression of genes coding for proteasomal proteins as well as in post-stroke aged Sprague-Dawley rats exposed to H2S- induced hypothermia.
Two days exposure to mild hypothermia diminishes the expression of several genes involved in protein degradation, thereby leading to better preservation of infarcted tissue. Further, hypothermia increased the density of newly formed blood vessels in the peri-lesional cortex did not enhance neurogenesis in the infarcted area of aged rats. Likewise, there was improved recovery of fine vestibulomotor function and asymmetric sensorimotor deficit.
Long-term hypothermia may be a viable clinical approach by simultaneously targeting multiple processes including better tissue preservation, enhanced vascular density and improved behavioral performance.
在老年人群中，中风是导致残疾的主要原因，目前尚无神经保护措施。在局灶性缺血的动物研究中，短期低温常可减小梗死面积。然而，有效的神经保护需要长期、可控地降低体温。此前，我们报道中风后暴露于硫化氢（H₂S）可有效降低老年动物的体温并提供神经保护。
在本研究中，我们使用行为测试、MRI、遥测脑电图、血压和体温记录、RT-PCR以及免疫荧光技术，评估了暴露于H₂S诱导低温的中风后老年Sprague-Dawley大鼠的梗死面积、血管密度、神经发生以及编码蛋白酶体蛋白的基因表达。
两天的轻度低温暴露可减少参与蛋白质降解的几种基因的表达，从而更好地保存梗死组织。此外，低温增加了病灶周围皮质新生血管的密度，但并未增强老年大鼠梗死区域的神经发生。同样，精细前庭运动功能和不对称感觉运动缺陷的恢复也有所改善。
长期低温可能是一种可行的临床方法，可同时针对多个过程，包括更好地保存组织、增强血管密度和改善行为表现。
