Systemic hyperthermia induces ischemic brain injury in neonatal mice with ligated carotid artery and jugular vein.
Postnatal d 7 (p7) or p12 mice had their right carotid artery (CA) and jugular vein (JV) ligated to mimic veno-arterial (VA) access for extracorporeal membrane oxygenation (ECMO). At p9-11 (early) or p19-21 (late) mice were exposed to hyperthermia or normothermia followed by assessment of neuropathological injury score. In separate cohorts of mice, cerebral and peripheral blood flow (CBF, PBF) and cerebral ATP content was measured. Hyperthermia resulted in ischemic brain injury in 57% and 77% of mice subjected to early or late hyperthermia, respectively. Isolated CA+JV ligation induced minimal injury (score 0.47 +/- 0.34) in 2/8 mice from the late normothermia group. No cerebral injury was detected in mice subjected to early normothermia. In 3/19 shams (2/10 early, 1/9 late) hyperthermia induced a subtle (score, 0.6 +/- 0.27) injury in the ipsilateral to the site of surgery cortex. CBF and PBF increased in response to hyperthermia in all mice. The rise in CBF was significantly attenuated in the "ligated" versus intact hemisphere, which was associated with a profound depletion of ATP content. Systemic hyperthermia induces ischemic brain injury in mice with ligated CA+JV. We speculate that hyperthermia/fever can be a potential risk factor for brain injury in infants treated with VA ECMO.
Slinko
Siarhei
S
Department of Pediatrics, Division of Neonatology, Columbia University, New York, New York 10032, USA.
Caspersen
Casper
C
Ratner
Veniamin
V
Kim
Jin-Ji
JJ
Alexandrov
Paul
P
Polin
Richard
R
Ten
Vadim S
VS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001831:Body Temperature; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology; D002339:Carotid Arteries / Q000601:surgery*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D002560:Cerebrovascular Circulation; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D005334:Fever; D006801:Humans; D007601:Jugular Veins / Q000601:surgery*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012039:Regional Blood Flow
D000255:Adenosine Triphosphate