Nyberg Christoffer, Karlsson Torbjörn, Hillered Lars, Ronne Engström Elisabeth
Department of Neuroscience, section of Neurosurgery, Uppsala University, Uppsala, Sweden.
Department of Surgical Sciences, section of Anesthesiology and Intensive care, Uppsala University, Uppsala, Sweden.
PLoS One. 2014 Jun 18;9(6):e99904. doi: 10.1371/journal.pone.0099904. eCollection 2014.
Aneurysmal subarachnoid hemorrhage (SAH) may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed.
To study early cerebral energy changes in an animal model.
Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate.
In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia.
The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.
动脉瘤性蛛网膜下腔出血(SAH)可导致脑缺血及包括应激反应在内的全身反应。为研究动脉瘤破裂后的即刻脑和全身变化,需要动物模型。
在动物模型中研究早期脑能量变化。
通过向猪的前颅底注射自体血诱导实验性SAH,同时控制颅内压和脑灌注压。采用脑微透析监测葡萄糖、丙酮酸和乳酸的浓度。
9只猪出现短暂性缺血模式,注血后不久脑灌注压急剧下降,同时葡萄糖和丙酮酸迅速减少。随后乳酸增加,丙酮酸延迟增加,导致乳酸/丙酮酸比值显著但短暂升高。此后葡萄糖、丙酮酸、乳酸及乳酸/丙酮酸比值恢复至基线水平。其余2只猪代谢反应更严重,葡萄糖和丙酮酸迅速降至无法检测水平,而乳酸增加并持续升高,提示持续性缺血。
该动物模型不仅通过血液在基底池沉积模拟SAH情况,还产生了动脉瘤性SAH的短暂性全脑缺血影响。脑代谢变化提示即刻短暂的底物衰竭,随后再灌注时葡萄糖出现高代谢。该模型具有类似自发性出血的特征,适用于未来对SAH早期脑和全身反应的研究,而这些反应在人类中难以研究。