Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia

• Published in: Annals of neurology Vol. 58; no. 1; pp. 75 - 87
• Main Authors: Iwata, Osuke, Thornton, John S., Sellwood, Mark W., Iwata, Sachiko, Sakata, Yasuko, Noone, Martina A., O'Brien, Frances E., Bainbridge, Alan, De Vita, Enrico, Raivich, Gennadij, Peebles, Donald, Scaravilli, Francesco, Cady, Ernest B., Ordidge, Roger, Wyatt, John S., Robertson, Nicola J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2005; Willey-Liss
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Disease Models, Animal; Female; Hypothermia, Induced; Hypoxia-Ischemia, Brain - pathology; Hypoxia-Ischemia, Brain - therapy; Male; Medical sciences; Nerve Degeneration - prevention & control; Neurology; Neurons - pathology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Swine; Temperature; Vascular diseases and vascular malformations of the nervous system; Oxygen; Nervous system diseases; Cooling; Ischemia; Cardiovascular disease; Hypoxia; Depth
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.20528

Hypothermia after perinatal hypoxia‐ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham‐normothermia (38.5–39°C); (Group ii) sham‐33°C; (Group iii) HI‐normothermia; (Group iv) HI‐35°C; and (Group v) HI‐33°C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35°C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33°C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33°C, 35°C resulted in more viable neurons in deep GM, whereas 33°C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient‐specific hypothermia protocols by combining systemic and selective cooling. Ann Neurol 2005;58:75–87