Sharma A C, Misra M, Prat R, Alden K, Sam A D, Markiv V Z, Dujovny M, Ferguson J L
Department of Physiology & Biophysics, University of Illinois College of Medicine at Chicago 60612-7342, USA.
Neurol Res. 1998 Oct;20(7):632-6. doi: 10.1080/01616412.1998.11740575.
In the present study, we hypothesized that acute diffuse brain injury (DBI) in rats would produce an increase in endothelin-1 (ET-1), a potent vasoconstrictor, and/or nitric oxide (NO), a potent vasodilator, in plasma and brain areas in rats. DBI was induced in anesthetized male Sprague-Dawley rats (350-400 g) using a 350 g weight dropped from 1 meter height impact through a device designed by Marmarou et al., 1994. Blood plasma and brain tissue (cerebral cortex, diencephalon and brain stem) samples were collected for estimation of ET-1 and NO at zero or 6 h from rats (n = 6) subjected to DBI as well as control rats (n = 6), i.e., not subjected to DBI. In a separate group of animals, cerebral blood flow (CBF) was recorded at 0, 5, 10, 15, 30, 60, 120, 240 and 360 min after induction of DBI or sham-DBI. Acute DBI produced a significant decrease in CBF at 120 min after induction of DBI. Plasma levels of ET-1 was found to be significantly increased (from 0.89 +/- 0.09 to 2.09 +/- 0.29 pg ml-1), at 6 h following DBI. DBI produced a significant decrease in the levels of ET-1 in diencephalon (from 70.97 +/- 9.47 to 57.64 +/- 2.65 pg g-1). In contrast to ET-1, DBI produced a significant increase in the concentrations of NO in the diencephalon, cerebral cortex and brain stem at 6 h post DBI. It appears that DBI-induced increase in the levels of NO in brain regions which might be down regulating the synthesis of ET-1 in diencephalon. It is concluded that ET and NO homeostatic mechanisms may play a role in the regional and vascular responses associated with acute DBI.
在本研究中，我们假设大鼠急性弥漫性脑损伤（DBI）会导致血浆和脑区中强效血管收缩剂内皮素-1（ET-1）和/或强效血管舒张剂一氧化氮（NO）增加。使用Marmarou等人1994年设计的装置，将350克重物从1米高度落下撞击麻醉的雄性Sprague-Dawley大鼠（350 - 400克）来诱导DBI。在DBI处理的大鼠（n = 6）以及对照大鼠（n = 6）（即未接受DBI处理）的0小时或6小时时，采集血浆和脑组织（大脑皮层、间脑和脑干）样本，用于评估ET-1和NO。在另一组动物中，在诱导DBI或假手术DBI后的0、5、10、15、30、60、120、240和360分钟记录脑血流量（CBF）。急性DBI在诱导后120分钟时导致CBF显著降低。发现DBI后6小时血浆ET-1水平显著升高（从0.89±0.09升高至2.09±0.29 pg ml-1）。DBI使间脑中ET-1水平显著降低（从70.97±9.47降至57.64±2.65 pg g-1）。与ET-1相反，DBI在DBI后6小时使间脑、大脑皮层和脑干中的NO浓度显著增加。似乎DBI诱导的脑区NO水平升高可能下调了间脑中ET-1的合成。结论是，ET和NO稳态机制可能在与急性DBI相关的区域和血管反应中起作用。
