Steven Miller: When Injury Happens: Imaging the Newborn Brain ...
Steven Miller: When Injury Happens: Imaging the Newborn Brain ...
Steven Miller: When Injury Happens: Imaging the Newborn Brain ...
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Opportunities for Intervention<br />
Fractional No Postoperative Preoperative<br />
Anisotropy <strong>Injury</strong> <strong>Injury</strong> <strong>Injury</strong> P<br />
% Increase/week<br />
Median Median<br />
Median<br />
DTT: 4.43 2.44 0.90 0.02*<br />
Ferriero DM NEJM 2006<br />
Neurotoxic Cascade in Hypoxia<br />
Ischemia<br />
Cerebral blood flow<br />
Energy failure<br />
Hypo<strong>the</strong>rmia<br />
Hypo<strong>the</strong>rmia: protects cortex<br />
Glutamate release<br />
Calcium-dependent<br />
‘excitotoxicity’<br />
Apoptotic cell death<br />
Caspase inhibitors<br />
Delayed cell death<br />
Anti-inflammatory agents<br />
NMDA-2nd messenger<br />
modulation<br />
Necrotic cell death<br />
Inflammation<br />
Repair<br />
Restoration<br />
Neurotrophins<br />
Plasticity & Recovery<br />
Stem cells<br />
Normo<strong>the</strong>rmia<br />
Hypo<strong>the</strong>rmia<br />
Inder TE et al. J Pediatr 2004; 145:835-7<br />
Blockade of NMDA Receptor Leads to<br />
Apoptotic Cell Death in Neonatal Rats<br />
• P7 rats<br />
• 3 IP injections of<br />
MK801<br />
• Sacrificed 24 hours<br />
post injection<br />
• Silver stain to detect<br />
apoptotic cells<br />
Conclusions<br />
• Timing informs mechanism<br />
• Surprising patterns of brain injury<br />
• Consider brain development<br />
• <strong>Imaging</strong> important for implementing<br />
brain protection<br />
Ikonomidou, C et. al (1999) Science 283:70-74<br />
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