Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Feb 2012
Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage.
It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. ⋯ Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.
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J. Cereb. Blood Flow Metab. · Jan 2012
Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma.
Traumatic brain injury (TBI) induces secondary injury mechanisms, including cell-cycle activation (CCA), which lead to neuronal cell death, microglial activation, and neurologic dysfunction. Here, we show progressive neurodegeneration associated with microglial activation after TBI induced by controlled cortical impact (CCI), and also show that delayed treatment with the selective cyclin-dependent kinase inhibitor roscovitine attenuates posttraumatic neurodegeneration and neuroinflammation. CCI resulted in increased cyclin A and D1 expressions and fodrin cleavage in the injured cortex at 6 hours after injury and significant neurodegeneration by 24 hours after injury. ⋯ Central administration of roscovitine at 3 hours after CCI reduced subsequent cyclin A and D1 expressions and fodrin cleavage, improved functional recovery, decreased lesion volume, and attenuated hippocampal and cortical neuronal cell loss and cortical microglial activation. Furthermore, delayed systemic administration of roscovitine improved motor recovery and attenuated microglial activation after CCI. These findings suggest that CCA contributes to progressive neurodegeneration and related neurologic dysfunction after TBI, likely in part related to its induction of microglial activation.
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J. Cereb. Blood Flow Metab. · Nov 2011
Validating a local Arterial Input Function method for improved perfusion quantification in stroke.
In bolus-tracking perfusion magnetic resonance imaging (MRI), temporal dispersion of the contrast bolus due to stenosis or collateral supply presents a significant problem for accurate perfusion quantification in stroke. One means to reduce the associated perfusion errors is to deconvolve the bolus concentration time-course data with local Arterial Input Functions (AIFs) measured close to the capillary bed and downstream of the arterial abnormalities causing dispersion. Because the MRI voxel resolution precludes direct local AIF measurements, they must be extrapolated from the surrounding data. ⋯ The local AIF methods reduced dispersion in the majority of data sets, suggesting more accurate perfusion quantification. Importantly, the validation inherently identifies potential areas for perfusion underestimation. This is valuable information for the identification of at-risk tissue and management of stroke patients.
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J. Cereb. Blood Flow Metab. · Sep 2011
CSF Bcl-2 and cytochrome C temporal profiles in outcome prediction for adults with severe TBI.
The biochemical cascades associated with cell death after traumatic brain injury (TBI) involve both pro-survival and pro-apoptotic proteins. We hypothesized that elevated cerebrospinal fluid (CSF) Bcl-2 and cytochrome C (CytoC) levels over time would reflect cellular injury response and predict long-term outcomes after TBI. Cerebrospinal fluid Bcl-2 and CytoC levels were measured for 6 days after injury for adults with severe TBI (N=76 subjects; N=277 samples). ⋯ Subjects with Bcl-2 profiles that remained near controls had better outcomes than those with consistently elevated Bcl-2 profiles. However, subjects with Bcl-2 values that started near controls and steadily rose over time had 100% good outcomes by 12 months after TBI. These results show the prognostic value of Bcl-2 and CytoC profiles and suggest a dynamic apoptotic and pro-survival response to TBI.
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J. Cereb. Blood Flow Metab. · Sep 2011
Therapeutic hypothermia alters microRNA responses to traumatic brain injury in rats.
Therapeutic hypothermia promotes protection after traumatic brain injury (TBI). The mechanisms underlying hypothermic protection are multifactorial and may include the modulation of microRNA (miRNA) expression after trauma. We utilized microarrays to examine the effects of posttraumatic hypothermia on the expression of 388 rat miRNAs. ⋯ Regionally specific miRNAs also showed responses to TBI and hypothermia treatments by in situ hybridization. In addition, in vitro neuronal stretch injury studies showed similar temperature-sensitive responses to specific miRNAs. These novel data indicate that the reported beneficial effects of early hypothermia on traumatic outcome may include temperature-sensitive miRNAs involved in basic cell-processing events.