Enhanced Microdialysis for CSD Monitoring

 描述（由申请人提供）：脑损伤引起皮质扩散性抑制现象。 在健康的大脑中，扩散性抑郁与偏头痛有关，但不知道会导致脑损伤。 在受伤的大脑中，复发性扩散性抑郁导致继发性脑损伤，并与原发性损伤后6个月的不良患者结局（包括死亡、植物人状态或严重残疾）显著相关。 脑损伤患者的微透析显示，扩散性抑制消耗脑葡萄糖，反映了去极化波通过后对能量的突然和强烈需求，以驱动脑组织的ATP依赖性复极。 通过血流输送的葡萄糖不能跟上需求的步伐，脑组织变得缺乏葡萄糖。 这种葡萄糖剥夺与危险半影组织的继发性损伤有关，导致损伤核心扩大。 目前，临床微透析不用于评估扩散性抑郁症的代谢严重程度，由于结果的变异性。 本课题的目的是在实验动物中开发“地塞米松强化微透析”，作为消除微透析探针部位缺血和胶质增生的方法，从而提高可靠性。 在损伤后1-10天的临床相关时间窗内进行微透析测量。

 DESCRIPTION (provided by applicant): Brain injury gives rise to the phenomenon of cortical spreading depression. In healthy brain, spreading depressions are associated with migraine but are not known to cause brain damage. In the injured brain, recurrent spreading depressions lead to secondary brain injury and correlate significantly with poor patient outcomes including death, vegetative state, or severe disability 6 months after the primary injury. Microdialysis in patients with brain injury shows that spreading depressions deplete brain glucose, reflecting the sudden and intense demand for energy to drive ATP-dependent repolarization of brain tissue after the depolarization wave passes. Glucose delivery via the blood flow fails to keep pace with the demand and brain tissue becomes glucose deprived. This glucose deprivation is implicated in secondary injury to the at-‐risk penumbral tissue, resulting in expansion of the injury core. At present, clinical microdialysis is not used to assess the metabolic severity of spreading depressions due to variability in the results. The objective of this project is to develop, in experimental animals, "dexamethasone-enhanced microdialysis" as an approach to eliminate ischemia and gliosis at the microdialysis probe site and thereby improve the reliability of microdialysis measurements over the 1-10 day clinically relevant time window post-injury.