Previous studies indicated preconditioning of the brain with sublethal ischemic insults separated by many hours, protected tissues from a subsequent lethal insult. We recently reported neuroprotection by a rapid preconditioning paradigm where a sublethal ischemic insult preceded test ischemia by only 30 min. We hypothesize that neuroprotection caused by the rapid ischemic preconditioning (IPC) will result in lowered microglial, reactive astrocytes and increased normal neuronal cell counts. Wistar rats underwent normothermic (36.5-37 degrees C) global cerebral ischemia, produced by bilateral carotid artery ligation after lowering mean systemic blood pressure. The preconditioning ischemic insult lasted 2 min and was associated with a sufficient amount of time to provoke anoxic depolarization. After a 30-min reperfusion period, 10-min test ischemia was produced, and histopathology was assessed 3 and 7 days later. Normal neuronal cell counts for control rats at 3 days survival were significantly lower (by 58%) than in IPC animals. Although there was a trend toward protection in IPC rats at 7 days, the difference in normal neuronal cell count between the IPC and control groups was not significant. IPC rats at 3 days but not 7 days of survival showed a significantly lower microglial cell count (by 56%) than control rats. These results showed that the protection induced through IPC at 3 days of survival produced lower numbers of microglia, while maintaining normal neuronal cells. No significant differences between control and IPC groups were found in astrocytic cell count at any time of reperfusion in any region of the hippocampus studied. The beneficial effects of IPC may, therefore, involve anti-inflammatory processes that target microglial activation after cerebral ischemia.

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It was an honor for me to present the 2014 G. Heiner Sell Memorial Lecture at the annual American Spinal Injury Association (ASIA) meeting in San Antonio. For this purpose, I provided a comprehensive review of the scope of research targeting discovery and translational and clinical investigations into spinal cord injury (SCI) research. Indeed, these are exciting times in the area of spinal cord research and clinical initiatives. Many laboratories and clinical programs throughout the world are publishing data related to the pathophysiology of SCI and new strategies for protecting and promoting recovery in both animal models and humans. For this lecture, several topics were discussed including neuroprotective and reparative strategies, neurorehabilitation, quality of life issues, and future directions. In the area of neuroprotection, pathophysiological events that may be targeted with therapeutic strategies, including pharmacological and targeted temperature management were reviewed. For reparative approaches, the importance of both intrinsic and extrinsic mechanisms of axonal regeneration was highlighted. Various cell therapies currently being tested in preclinical and clinical arenas were reviewed as well as ongoing US Food and Drug Administration approved trials for SCI patients. Neurorehabilitation is an evolving research field with locomotive training strategies, electrical stimulation, and brain-machine interface programs targeting various types of SCI. The importance of testing combination approaches including neuroprotective, reparative, and rehabilitative strategies to maximize recovery mechanisms was therefore emphasized. Finally, quality of life issues that affect thousands of individuals living with paralysis were also presented. Future directions and specific obstacles that require attention as we continue to move the SCI field forward were discussed.