The Adverse Pial Arteriolar and Axonal Consequences of Traumatic Brain Injury Complicated by Hypoxia and Their Therapeutic Modulation with Hypothermia in Rat

Abstract

This study examined the effect of posttraumatic hypoxia on cerebral vascular responsivity and axonal damage, while also exploring hypothermia's potential to attenuate these responses. Rats were subjected to impact acceleration injury (IAI) and equipped with cranial windows to assess vascular reactivity to topical acetylcholine, with postmortem analyses using antibodies to amyloid precursor protein to assess axonal damage. Animals were subjected to hypoxia alone, IAI and hypoxia, IAI and hypoxia before induction of moderate hypothermia (33 degrees C), IAI and hypoxia induced during hypothermic intervention, and IAI and hypoxia initiated after hypothermia. Hypoxia alone had no impact on vascular reactivity or axonal damage. Acceleration injury and posttraumatic hypoxia resulted in dramatic axonal damage and altered vascular reactivity. When IAI and hypoxia were followed by hypothermic intervention, no axonal or vascular protection ensued. However, when IAI was followed by hypoxia induced during hypothermia, axonal and vascular protection followed. When this same hypoxic insult followed the use of hypothermia, no benefit ensued. These studies show that early hypoxia and delayed hypoxia exert damaging axonal and vascular consequences. Although this damage is attenuated by hypothermia, this follows only when hypoxia occurs during hypothermia, with no benefit found if the hypoxic insult proceeds or follows hypothermia.