An opportune time for targeted brain arteriovenous malformation therapy.
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Journal Article↗
Biomedical subjects
MingMing Ning
Publications and source records attributed to MingMing Ning.
Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke.
Reperfusion therapy with tissue plasminogen activator (tPA) is a rational therapy for acute ischemic stroke. Properly titrated use of tPA improves clinical outcomes. However, there is also an associated risk of hemorrhagic transformation after tPA therapy. Emerging data now suggest that some of these potentially neurotoxic side effects of tPA may be due to its signaling actions in the neurovascular unit. Besides its intended role in clot lysis, tPA is also an extracellular protease and signaling molecule in brain. tPA mediates matrix remodeling during brain development and plasticity. By interacting with the NMDA-type glutamate receptor, tPA may amplify potentially excitotoxic calcium currents. At selected concentrations, tPA may be vasoactive. Finally, by augmenting matrix metalloproteinase (MMP) dysregulation after stroke, tPA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema, and hemorrhage. Understanding these pleiotropic actions of tPA may reveal new therapeutic opportunities for combination stroke therapy.
Animals↗
Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage.
BACKGROUND AND PURPOSE: Small asymptomatic cerebral hemorrhages detectable by gradient-echo MRI are common in patients with intracerebral hemorrhage (ICH), particularly lobar ICH related to cerebral amyloid angiopathy (CAA). We sought to determine whether hemorrhages detected at the time of lobar ICH predict the major clinical complications of CAA: recurrent ICH or decline in cognition and function. METHODS: Ninety-four consecutive survivors of primary lobar ICH (age > or =55) with gradient-echo MRI at presentation were followed in a prospective cohort study for 32.9+/-24.0 months. A subset of 34 subjects underwent a second MRI after a stroke-free interval of 15.8+/-6.5 months. Study endpoints were recurrent symptomatic ICH or clinical decline, defined as onset of cognitive impairment, loss of independent functioning, or death. RESULTS: The total number of hemorrhages at baseline predicted risk of future symptomatic ICH (3-year cumulative risks 14%, 17%, 38%, and 51% for subjects with 1, 2, 3 to 5, or > or =6 baseline hemorrhages, P=0.003). Higher numbers of hemorrhages at baseline also predicted increased risk for subsequent cognitive impairment, loss of independence, or death (P=0.002) among subjects not previously demented or dependent. For subjects followed after a second MRI, new microhemorrhages appeared in 17 of 34 and predicted increased risk of subsequent symptomatic ICH (3-year cumulative risks 19%, 42%, and 67% for subjects with 0, 1 to 3, or > or =4 new microhemorrhages, P=0.02), but not subsequent clinical decline. CONCLUSIONS: Hemorrhages identified by MRI predict clinically important events in survivors of lobar ICH. Detection of microhemorrhages may be useful for assessing risk in ICH patients and as a surrogate marker for clinical studies.
Aged↗
Preventing a second stroke in the young.
In the United States, more than 220,000 adults under the age of 45 have had a stroke. Secondary stroke prevention is critical in this population because of the potential impact of a second stroke on productivity and future quality of life. In addition to conventional stroke risk factors, younger patients have special risk factors inherent to genetic and environmental elements, such as the use of illicit drugs and cardiac abnormalities; in women, risk factors include pregnancy, migraine, and the use of oral contraceptives.
Adult↗