Daniel T Laskowitz

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INTRODUCTION Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify(More)
BACKGROUND AND PURPOSE Endothelial nitric oxide synthase (eNOS) activity is decreased after subarachnoid hemorrhage (SAH). Simvastatin increases eNOS activity. We hypothesized that simvastatin would increase eNOS protein and ameliorate SAH-induced cerebral vasospasm. METHODS Mice were treated with subcutaneous simvastatin or vehicle for 14 days and then(More)
Human apolipoprotein E is the major apolipoprotein expressed in the brain and exists as three isoforms, designated E2, E3, and E4. Although evidence suggests that apolipoprotein E plays an important role in modifying systemic and brain inflammatory responses, there is little data investigating apoE isoform-specific effects in vivo. In this study, we(More)
BACKGROUND Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after noncardiac surgery. Identified risk factors are largely limited to demographic characteristics. We hypothesized that POCD was associated with apolipoprotein E4 (APOE4) genotype and plasma biomarkers of brain injury and inflammation. METHODS Three hundred(More)
BACKGROUND AND PURPOSE Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH. METHODS Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive(More)
Apolipoprotein E (apoE) is a 299 amino acid protein that is associated with risk of developing Alzheimer's Disease (AD) and outcome after acute brain injury. To investigate the possibility that apoE modulates glial activation we studied the effect of endogenous apoE on inflammatory gene regulation in vitro and in vivo. Our results indicate that apoE(More)
Apolipoprotein E plays an important role in recovery from acute brain injury and risk of developing Alzheimer's disease. We demonstrate that biologically relevant concentrations of apoE suppress microglial activation and release of TNFalpha and NO in a dose-dependent fashion. Peptides derived from the apoE receptor-binding region mimic the effects of the(More)
Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic disease. This experiment compared the neurologic and histologic outcome of ApoE-deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of middle cerebral artery filament occlusion and a recovery interval of 24 hours. With 60 minutes of ischemia, there was(More)
A central issue in the pathogenesis of tauopathy is the question of how tau protein dysfunction leads to neurodegeneration. We have previously demonstrated that the absence of tau protein is associated with destabilization of microtubules and impaired neurite outgrowth (Dawson et al., 2001; Rapoport et al., 2002). We now hypothesize that the absence of(More)
BACKGROUND AND PURPOSE The absence of a widely available and sensitive diagnostic test for acute cerebral ischemia remains a significant limitation in the diagnosis and management of stroke. The objective of this study was to examine the feasibility of developing a diagnostic panel of blood-borne biochemical markers of cerebral ischemia. METHODS Serial(More)