Mechanisms of ischemic injury in mammalian spinal cord
Abstract
This study examines the effects of ischemia, and ensuing subsequent cellular events, on mammalian spinal cord ventral white matter (VWM). Ischemia can act as a primary injury when there is an occlusion in the blood supply, but also arises following mechanical injury. Ischemia obstructs normal cellular metabolic functions by preventing the delivery of vital substrates such as oxygen and glucose. A key aspect of spinal cord physiology is its role in electric impulse propagation, and without normal metabolic function, spinal cord conduction becomes compromised. Utilizing a unique recording model, we are able to visual a real time recording of membrane electrophysiological activity (CAP, CMP, latency) and can observe the immediate effects of ischemia on conduction. We found that if we subject the VWM to an acute ischemic insult, they have the ability to recover almost 100% of their initial CAP. This model also enables us to isolate the ischemic insult due to the design of the recording apparatus. By isolating the ischemic insult, we are able to create artificial secondary injuries, by introducing relevant metabolic toxins that accumulate as a result of reperfusion of blood to the tissues. This reperfusion period is necessary for the survival of the tissue, but at the same time can lead to many detrimental metabolic events, such as FR production and LPO. In this study we examined the effects of acrolein, a toxic by-product of LPO. It was found that acrolein concentrations that are not harmful to healthy spinal cord, lead to conduction failure if introduced subsequent to ischemia. In addition, acrolein causes anatomical damage to VWM, as observed with HRP histology. Finally, we wanted to determine if we could develop a treatment protocol that could reverse some of the damaging effects of acrolein reperfusion. We pretreated the spinal cord with the ester form of glutathione, a powerful free radical scavenger and antioxidant, attempting to prevent the damaging effects of acrolein. We also treated the spinal cords with a high concentration of ascorbic acid during acrolein reperfusion. Both treatments proved effective in reducing the damaging effects of acrolein on the spinal cord tissue following ischemia.
Degree
Ph.D.
Advisors
Shi, Purdue University.
Subject Area
Neurology
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