Traumatic brain injury initiates several metabolic processes that can exacerbate the injury. There is evidence that hypothermia may limit some of these deleterious metabolic responses.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

The extent to which polymorphonuclear leukocytes and monocytes/macrophages contribute to the pathobiology of cerebral ischemia and stroke is an issue of long-standing contradiction and controversy. Recent developments in the ability to selectively modify leukocyte adhesion with antiadhesion antibodies and the potential clinical application of this therapeutic approach have spurred a resurgence of experimental studies examining the role of leukocytes in cerebral ischemia and stroke. We review studies examining leukocyte accumulation, initiation of thrombosis, and exacerbation of ischemic brain injury in stroke, and we examine other proposed contributions of leukocytes to cerebrovascular pathophysiology. The importance of specific characteristics of a given ischemia model and of underlying stroke risk factors in determining the degree of leukocyte involvement and effectiveness of therapies directed against these cells is discussed.

In an anesthetized canine model in which ischemia was induced by incremental air embolism, 16 animals were exposed to 1 hr of ischemia and monitored for 10 min (n = 4), 60 min (n = 6), or 240 min (n = 6). Fourteen animals were observed for corresponding periods without being subjected to ischemia 70 min (n = 4), 120 min (n = 4), or 300 min (n = 6). Autologous granulocytes were labeled with 111In and reinfused just before ischemia. At the conclusion of each experiment, a 14C-iodoantipyrine autoradiographic blood flow study was performed. Granulocyte accumulation measured by gamma scintigraphy (cpm/gm) occurred in the injured hemisphere of ischemic animals at 60 min in anterior brain segments and at 240 min in anterior, middle, and posterior segments. By means of a double-label autoradiography technique, clustering of punctate granulocyte images was detected in regions of low flow or heterogeneous flow in half of the animals at both 60 min and 240 min postischemia. Granulocyte clustering did not occur in the autoradiograms of nonischemic animals. The results implicate granulocyte participation in the acute phase of ischemic brain injury and signal a convergence of hemostatic and inflammatory processes during the immediate postischemic period.