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The importance of neutrophil influx in reperfusion injury has been demonstrated experimentally by the ability of anti-inflammatory interventions, such as treatment with antibodies that block cytokines or adhesion molecules, to reduce the extent of the injury. 33 The complement system is involved in host defense and is an important mechanism of immune injury (Chapter 6). 34 CHEMICAL (TOXIC) INJURY Chemical injury remains a frequent problem in clinical medicine and is a major limitation to drug therapy.
Several other caspases, including caspase-3 and caspase-6, serve as executioners. Like many proteases, caspases exist as inactive pro-enzymes, or zymogens, and must undergo an enzymatic cleavage to become active. The presence of cleaved, active caspases is a marker for cells undergoing apoptosis (Fig. 1–22C). We will discuss the roles of these enzymes in apoptosis later in this section. DNA and Protein Breakdown. 41 Subsequently, there is cleavage of DNA by Ca2+and Mg2+-dependent endonucleases into fragments whose sizes are multiples of 180 to 200 base pairs, reflecting cleavage between nucleosomal subunits.
The strategy that is perhaps the most useful in ischemic (and traumatic) brain and spinal cord injury is the transient induction of hypothermia (reducing the core body temperature to 92°F). This treatment reduces the metabolic demands of the stressed cells, decreases cell swelling, suppresses the formation of free radicals, and inhibits the host inflammatory response. 28 ISCHEMIA-REPERFUSION INJURY Restoration of blood flow to ischemic tissues can promote recovery of cells if they are reversibly injured.