Apparent reversal of early ischemic changes on non-contrast computed tomography following successful endovascular reperfusion.

Early ischemic changes seen on Non-contrast computed tomography (NCCT) secondary to cerebral edema is believed to indicate irreversible cellular injury. Computed tomography perfusion (CTP) may overpredict the infarct core in patients with large vessel occlusion (LVO) presenting in acute phase as these changes are potentially reversible if successful endovascular reperfusion is performed in a timely manner. This has led to the concept of "ghost infarct core" which is the mismatch in the infarct core as seen on follow-up imaging.

No Time to Lose: Cases of Anticoagulant Reversal Before Thrombolysis in Acute Ischemic Stroke Patients.

Direct oral anticoagulant (DOAC) reversal before intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients is well-documented in Europe, specifically for dabigatran: the selective humanized monoclonal antibody fragment idarucizumab, given to neutralize dabigatran prior to IVT, was associated with improved outcomes post-IVT. However, in the United States, this approach is rarely reported and not endorsed by guidelines. Therefore, further reporting on this is needed and neuroradiographic correlation may help validate this concept.

Immediate Transfer for Clot Extraction in a Young Woman With Leukemia and Asparaginase-Associated Acute Cerebral Vein Thrombosis.

We present the case of an 18-year-old woman with B-cell acute lymphoblastic leukemia (ALL) who developed hemorrhagic stroke and epilepsia partialis continua due to acute cerebral vein thrombosis (CVT). The patient had 10 risk factors for CVT (including use of asparaginase chemotherapy for the ALL) and also unfortunately had 4 biomarkers for poor prognosis for outcome post-CVT diagnosis. Immediate transfer to a Comprehensive Stroke Center allowed for hyperacute neurointerventional clot extraction with rapid restoration of the patency of the superior sagittal sinus.

In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH.

Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors.

Transient hypercapnia reveals an underlying cerebrovascular pathology in a murine model for HIV-1 associated neuroinflammation: role of NO-cGMP signaling and normalization by inhibition of cyclic nucleotide phosphodiesterase-5.

Background: Cerebral blood flow (CBF) is known to be dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. This is an important issue because impaired vasoreactivity has been associated with increased risk of ischemic stroke, elevated overall cardiovascular risk and cognitive impairment.

Methods: To test whether dysregulation of CBF might be due to virally-induced neuroinflammation, we used a well-defined animal model (GFAP-driven, doxycycline-inducible HIV-1 Tat transgenic (Tat-tg) mice).

Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response.

Quantification of nicotinamide adenine dinucleotide (NADH) changes during functional brain activation and pathological conditions provides critical insight into brain metabolism. Of the different imaging modalities, two-photon laser scanning microscopy (TPLSM) is becoming an important tool for cellular-resolution measurements of NADH changes associated with cellular metabolic changes. However, NADH fluorescence emission is strongly absorbed by hemoglobin.

Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease.

Mitochondrial superoxide flashes (mSOFs) are stochastic events of quantal mitochondrial superoxide generation. Here, we used flexor digitorum brevis muscle fibers from transgenic mice with muscle-specific expression of a novel mitochondrial-targeted superoxide biosensor (mt-cpYFP) to characterize mSOF activity in skeletal muscle at rest, following intense activity, and under pathological conditions. Results demonstrate that mSOF activity in muscle depended on electron transport chain and adenine nucleotide translocase functionality, but it was independent of cyclophilin-D-mediated mitochondrial permeability transition pore activity.

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions.

Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO(2) range with a p(50) of 3.

Cortical spreading depression causes and coincides with tissue hypoxia.

Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that has been implicated in migraine and in progressive neuronal injury after stroke and head trauma. Using two-photon microscopic NADH imaging and oxygen sensor microelectrodes in live mouse cortex, we find that CSD is linked to severe hypoxia and marked neuronal swelling that can last up to several minutes. Changes in dendritic structures and loss of spines during CSD are comparable to those during anoxic depolarization.

HIV-1 trans activator of transcription protein elicits mitochondrial hyperpolarization and respiratory deficit, with dysregulation of complex IV and nicotinamide adenine dinucleotide homeostasis in cortical neurons.

HIV-1 causes a common, progressive neurological disorder known as HIV-associated dementia (HAD). The prevalence of this disorder has increased despite the use of highly active antiretroviral therapy, and its underlying pathogenesis remains poorly understood. However, evidence suggests that some aspects of HAD may be reversible.

Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy.

Global analysis of fluorescence and associated anisotropy decays of intrinsic tissue fluorescence offers a sensitive and non-invasive probe of the metabolically critical free/enzyme-bound states of intracellular NADH in neural tissue. Using this technique, we demonstrate that the response of NADH to the metabolic transition from normoxia to hypoxia is more complex than a simple increase in NADH concentration. The concentration of free NADH, and that of an enzyme bound form with a relatively low lifetime, increases preferentially over that of other enzyme bound NADH species.

Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis.

We have found that two-photon fluorescence imaging of nicotinamide adenine dinucleotide (NADH) provides the sensitivity and spatial three-dimensional resolution to resolve metabolic signatures in processes of astrocytes and neurons deep in highly scattering brain tissue slices. This functional imaging reveals spatiotemporal partitioning of glycolytic and oxidative metabolism between astrocytes and neurons during focal neural activity that establishes a unifying hypothesis for neurometabolic coupling in which early oxidative metabolism in neurons is eventually sustained by late activation of the astrocyte-neuron lactate shuttle. Our model integrates existing views of brain energy metabolism and is in accord with known macroscopic physiological changes in vivo.

In vivo multiphoton microscopy of deep brain tissue.

Although fluorescence microscopy has proven to be one of the most powerful tools in biology, its application to the intact animal has been limited to imaging several hundred micrometers below the surface. The rest of the animal has eluded investigation at the microscopic level without excising tissue or performing extensive surgery. However, the ability to image with subcellular resolution in the intact animal enables a contextual setting that may be critical for understanding proper function.

Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy.

Microtubule (MT) ensemble polarity is a diagnostic determinant of the structure and function of neuronal processes. Here, polarized MT structures are selectively imaged with second-harmonic generation (SHG) microscopy in native brain tissue. This SHG is found to colocalize with axons in both brain slices and cultured neurons.