Karmacharya Mrigendra Bir, Kim Kil Hwan, Kim See Yoon, Chung Joonho, Min Byoung-Hyun, Park So Ra, Choi Byung Hyune
Department of Physiology, Inha University College of Medicine, Incheon, Korea.
Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
Neuropathol Appl Neurobiol. 2015 Jun;41(4):e80-94. doi: 10.1111/nan.12182.
Brain oedema is a major contributing factor to the morbidity and mortality of a variety of brain disorders. Although there has been considerable progress in our understanding of pathophysiological and molecular mechanisms associated with brain oedema so far, more effective treatment is required and is still awaited. Here we intended to study the effects of low intensity ultrasound (LIUS) on brain oedema.
We prepared the rat hippocampal slice in vitro and acute water intoxication in vivo models of brain oedema. We applied LIUS stimulation in these models and studied the molecular mechanisms of LIUS action on brain oedema.
We found that LIUS stimulation markedly inhibited the oedema formation in both of these models. LIUS stimulation significantly reduced brain water content and intracranial pressure resulting in increased survival of the rats. Here, we showed that the AQP4 localization was increased in the astrocytic foot processes in the oedematous hippocampal slices, while it was significantly reduced in the LIUS-stimulated hippocampal slices. In the in vivo model too, AQP4 expression was markedly increased in the microvessels of the cerebral cortex and hippocampus after water intoxication but was reduced in the LIUS-stimulated rats.
These data show that LIUS has an inhibitory effect on cytotoxic brain oedema and suggest its therapeutic potential to treat brain oedema. We propose that LIUS reduces the AQP4 localization around the astrocytic foot processes thereby decreasing water permeability into the brain tissue.
脑水肿是多种脑部疾病发病和死亡的主要促成因素。尽管到目前为止我们对与脑水肿相关的病理生理和分子机制的理解有了相当大的进展，但仍需要更有效的治疗方法，且这种方法仍有待探索。在此，我们旨在研究低强度超声（LIUS）对脑水肿的影响。
我们制备了体外大鼠海马切片和体内急性水中毒脑水肿模型。我们在这些模型中应用LIUS刺激，并研究LIUS作用于脑水肿的分子机制。
我们发现LIUS刺激在这两种模型中均显著抑制了水肿形成。LIUS刺激显著降低了脑含水量和颅内压，从而提高了大鼠的存活率。在此，我们表明，在水肿的海马切片中，水通道蛋白4（AQP4）在星形胶质细胞足突中的定位增加，而在LIUS刺激的海马切片中则显著降低。在体内模型中也是如此，水中毒后大脑皮层和海马微血管中的AQP4表达明显增加，但在LIUS刺激的大鼠中则降低。
这些数据表明LIUS对细胞毒性脑水肿具有抑制作用，并提示其治疗脑水肿的潜在可能性。我们认为，LIUS减少了星形胶质细胞足突周围的AQP4定位，从而降低了水进入脑组织的通透性。
