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Cerebrospinal fluid (CSF) adrenomedullin (ADM) levels are increased in female, but remain unchanged in male, piglets after fluid percussion injury (FPI) of the brain. Subthreshold vascular concentrations of ADM restore impaired hypotensive pial artery dilation after FPI more in males than females. Extracellular signal-related kinase (ERK) mitogen-activated(More)
Outcome of traumatic brain injury (TBI) is impaired by hyperglycemia, hypotension, and glutamate, and improved by insulin. Insulin reduces glutamate concentration, making it uncertain whether its beneficial effect accrues from euglycemia. Glucagon decreases CNS glutamate, lessens neuronal cell injury, and improves neurological scores in mice after TBI. In(More)
OBJECTIVE Traumatic brain injury contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after traumatic brain injury. Extracellular signal-related kinase mitogen-activated protein kinase is upregulated and reduces cerebral blood flow after fluid percussion brain injury in(More)
Traumatic brain injury (TBI) contributes to morbidity in children and boys, and hypotension worsens outcome. Extracellular signal-related kinase (ERK) mitogen-activated protein kinase (MAPK) is upregulated more in males and reduces cerebral blood flow (CBF) after fluid percussion injury (FPI). Increased cerebral perfusion pressure (CPP) via phenylephrine(More)
Traumatic brain injury (TBI) is a leading cause of morbidity in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Previous studies show that adrenomedullin, a cerebrovasodilator, prevented sex dependent impairment of autoregulation during hypotension after piglet fluid percussion brain injury (FPI).(More)
Stroke is a leading cause of morbidity and mortality. While tissue-type plasminogen activator (tPA) remains the only FDA-approved treatment for ischemic stroke, clinical use of tPA has been constrained to roughly 3% of eligible patients because of the danger of intracranial hemorrhage and a narrow 3 h time window for safe administration. Basic science(More)
Babies experience hypoxia (H) and ischemia (I) from stroke. The only approved treatment for stroke is fibrinolytic therapy with tissue-type plasminogen activator (tPA). However, tPA potentiates H/I-induced impairment of responses to cerebrovasodilators such as hypercapnia and hypotension, and blockade of tPA-mediated vasoactivity prevents this deleterious(More)
OBJECTIVE N-methyl-D-aspartate (NMDA)-induced pial artery dilation (PAD) is reversed to vasoconstriction after fluid percussion brain injury (FPI). Tissue type plasminogen activator (tPA) is up-regulated and the tPA antagonist, EEIIMD, prevents impaired NMDA PAD after FPI. Mitogen-activated protein kinase (MAPK), a family of at least three kinases, ERK,(More)
The sole FDA-approved treatment for acute stroke is recombinant tissue-type plasminogen activator (rtPA). However, rtPA aggravates the impairment of cerebrovasodilation induced by global hypoxia/ischemia; this impairment is attenuated by the preinjury treatment with the plasminogen activator inhibitor derivative EEIIMD. MAPK (a family of kinases, p38, and(More)
OBJECTIVE Pediatric ischemic stroke is a poorly understood, yet clinically important, problem. The sole approved treatment for acute stroke is tissue-type plasminogen activator. However, tissue plasminogen activator vasoactivity aggravates hypoxia/ischemia-induced impairment of cerebrovasodilation in response to hypercapnia and hypotension in newborn pigs.(More)