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The Protective Effects And Its Mechanism Of Rapid Ischemic Preconditioning Against Spinal Cord Ischemic Injury

Posted on:2005-12-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:H F SangFull Text:PDF
GTID:1104360122995805Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Spinal cord ischemic injury resulting in paraplegia remains a disastrous complication after operation on thoracoabbdominal aorta. The incidences of paraplegia range from 4% to 33%. Various methods of spinal cord protection, such as distal aortic perfusion, cerebrospinal fluid drainage , hypothermia and neuroprotective agents , have been suggested. However, none of these methods has totally prevented this complication. Therefore, it is an urgent task to find new strategies for spinal cord protection. Ischemic preconditioning(IPC) is an endogenous protective phenomenon in which a brief period of nonlethal ischemia increases the tolerance of the tissue to a subsequent lethal ischemia. Although IPC has been demonstrated to have protective effects on spinal cord ischemic injury, most of these studies focused on the delayed phase of IPC, defined that the reperfusion interval between the IPC and the subsequent ischemic event is not less than 12h; a few studies have investigated the spinal cord protection ofrapid phase of IPC, defined that the reperfusion interval between the IPC and the subsequent ischemic event is not more than 2h. Operation on tempory aorta occlusion within short time after IPC is feasible, so rapid IPC has clinical application value. To date, we know of no published studies about the mechanism of rapid IPC in spinal cord. This studies were designed to explore the protective effects and its mechanism of rapid IPC on spinal cord ischemic injury, providing evidence of clinical application for the rapid IPC and new strategies of spinal cord protection for pharmacological agents.The first part Experiment one Aim: To investigate the effect of different time of abdominal aorta occlusion on the intensity of spinal cord ischemic injury in rabbits, searching for a suitable time of spinal cord ischemic to establish basis for next experiments. Methods: The rabbits spinal cord ischemia was induced by occluding infrarenal abdominal aorta. 30 New Zealands white rabbits were assigned to five groups(n=6) as follows: abdominal aorta occlusion for 10min (I10), 20min (I2o)> 30min (ho)-. 40min (Uo) and Sham group respectively. The Sham group only underwent the exposure of the aorta. The neurologic function was assessed at 4, 8, 12., 24 and 48 h after reperfusion by using Tarlov Criteria: Grade 0, no voluntary hind-limb function; Grade 1, movement of joints perceptible; Grade 2, active movement but unable to stand; Grade 3, able to stand but unable to hop; Grade 4, normal hind-limb motor function. After the assessment, the spinal cord (L5-L7 )were harvested and the sections were stained by HE and TUNEL. Normal neurons in the anterior spinal cord were counted by means of light microscopy and apoptosis of neurons in the anterior spinal cord were assessed by TUNEL. Results: Rabbits in I40 group always showed paraplegia (grade 0) throughout the observation period;rabbits in I10 group all were normal (grade 4) except for one animal; the neurologic function of rabbits in bo and 130 groups was between IIQ and 140 groups. Under light microscopy, the rabbits in Lto group showed severe spinal cord injury with extensive vacuolation of gray matter while the rabbits in Iio group showed slight injury; the intensity of injury in bo and bo groups was between Iioand I40 groups. The scores of neurologic function and the number of normal neurons of anterior spinal cord in IIQgroup showed no significant differences with those in Sham group ( P >0.05), but were more than those in the other groups. The scores of neurologic function and the number of normal neurons of anterior spinal cord in bo group were similar with those in bo group (P >0.05), but were more than those in LJO groups. There are almost no TUNEL positive neurons of anterior spinal cord in LW and Sham groups; The TUNEL positive neurons of anterior spinal cord in bo group were more than that in 140 and Sham groups, but were similar with those in Iio and bo groups( P >0.05). Conclusion: The rabbits in Iio group which showed slight spinal cord injury were not suitable model to...
Keywords/Search Tags:rapid ischemic preconditioning, spinal cord, ischemic and reperfusion injury, adenosine A1 receptor, rabbits, rats.
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