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Armstead, William
1. tPA Variant tPA-S481A prevents impairment of cerebral autoregulation during hypotension and histopathology after TBI William M. Armstead, John Riley, Serge Yarovoi, Douglas B. Cines, Douglas H. Smith, and Abd Al-Roof Higazi Departments of Anesthesiology and Critical Care, Pharmacology, Pathology, and Neurosurgery University of Pennsylvania
2. Freeman, Udomphorn, Armstead, Fisk, Vavilala Anesthesiology 108: 588-595, 2008. Impairment of autoregulation correlates with GCS Impaired Cerebral Autoregulation MAP or CPP CBF (ml/100g/min) Intact Cerebral Autoregulation MAP or CPP CBF (ml/100g/min)
3. Cerebral autoregulation (ARI) is more impaired after moderate-severe TBI in children < 4 years. Glasgow outcome score (6 month GOS) is worse after moderate-severe TBI in children < 4 yrs. Freeman, Udomphorn, Armstead, Fisk, Vavilala Anesthesiology 108: 588-595, 20008 0.001 23 3 ARI > 0 (intact autoregulation) 5 8 ARI = 0 (absent autoregulation) 0.65 ± 0.31 0.33 ± 0.32 Mean ARI p Age ≥ 4 ( 12 ± 3) years (n=27) Age < 4 (2 ± 1) years (n=11) Table 2: 0.005 17 3 Age > 4 years 6 7 Age < 4 years p 6 month GOS > 4 (n=23) 6 month GOS < 4 (n=10) Table 4:
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5. tPA contributes to impaired NMDA cerebrovasodilation through activation of JNK and ERK MAPK. Neurologic Res, in press. Impaired NMDA receptor mediated cerebrovasodilation contributes to disturbed autoregulation during hypotension after TBI. Develop Brain Res 139: 19-28, 2002.
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8. FPI produces pial artery vasoconstriction, which was Blocked by tPA-S481A (1 mg/kg iv) 30 min post injury Pial artery dilation during hypotension blunted after FPI, but tPA-S481A prevented such impairment.
9. FPI was associated with marked neuronal cell loss in CA1 and CA3 hippocampus, which was prevented by tPA-S481A
