Changes in [18F]Fluorodeoxyglucose Activities in a Shockwave-Induced Traumatic Brain Injury Model Using Lithotripsy.

We present a longitudinal study of cerebral metabolism using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a rat model of shockwave-induced traumatic brain injury (SW-TBI). Anesthetized rats received 5 or 10 SW pulses to the right anterior lateral or dorsal frontal regions using SW lithotripsy. Animals were scanned for FDG uptake at baseline, 3 h post-injury, and 3 days post-injury, using a small animal PET/computed tomography (CT) scanner. FDG uptake at all time-points was quantified as the ratio of brain activity relative to peripheral activity in the left ventricle (LV) in the heart (Abrain/ALV) for the entire brain, each hemisphere, and four cortices (motor, cingulate, somatosensory, and retrosplenial). The mixed-designed models analysis of variance (ANOVA) for the hemispheric and global FDG uptake ratio showed a significant effect of the time-of-scan (p = 0.038) and measured region (p = 6.12e-09). We also observed a significant effect of the time-of-scan (p = 0.046) and measured region (p = 2.28e-09) for the FDG uptake ratio in four cortical regions. None of the measurements (global or local) showed a significant effect for the number of SW pulses (5 or 10) or SW location (lateral or dorsal frontal regions). Our data suggest that SW-TBI causes hypermetabolism on the impact side of the rat brain at 3 h post-injury compared with the baseline measurements. However, the increase in FDG uptake by day 3 post-injury was not significant. Further studies on post-TBI metabolic changes are needed to understand better the pathophysiology of the injury.

A Modified Method for Creating Elastase-Induced Aneurysms by Ligation of Common Carotid Arteries in Rabbits and Its Effect on Surrounding Arteries.

BACKGROUND AND PURPOSE: Rabbit models of intracranial aneurysms are frequently used in pre-clinical settings. This study aimed to demonstrate an alternative, extravascular method for creating elastase-induced aneurysms, and how ligation of the right common carotid arteries (RCCA) can impact flow redistribution into left CCA (LCCA). METHODS: Elastase-induced aneurysms in 18 New Zealand rabbits (4.14 ± 0.314 kg) were created by applying 3-5 U of concentrated elastase solution to the exterior of the right and left CCA roots (RCCA and LCCA). After the induction of the aneurysm, the aneurysm was either kept intact to the rest of the corresponding CCA, severed from the rest of the CCA to allow for a free standing aneurysm, or was anchored to nearby tissue to influence the angle and orientation of the aneurysm with respect to the parent vessel. Ultrasound studies were performed before and after creation of aneurysms to collect blood flow measurements inside the aneurysm pouch and surrounding arteries. Prior to sacrificing the animals, computed tomography angiography studies were performed. Harvested aneurysmal tissues were used for histological analysis. RESULTS: Elastase-induced aneurysms were successfully created by the extravascular approach. Histological studies showed that the biological response was similar to human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Ultrasound measurements indicated that after the RCCA was ligated, blood flow significantly increased in the LCCA at one-month follow-up. CONCLUSION: An alternate method for creating elastase-induced aneurysms has been demonstrated. The novel aspects of our method allow for ligation of one or both common carotid arteries to create a single or bilateral aneurysm with an ability to control the orientation of the induced aneurysm.

Antiplatelet and Anticoagulant Therapies for Prevention of Ischemic Stroke.

Ischemic stroke represents one of the leading causes of death and disability in both the United States and abroad, particularly for patients with prior ischemic stroke or transient ischemic attack (TIA). A quintessential aspect of secondary stroke prevention is the use of different pharmacological agents, mainly antiplatelets and anticoagulants. Antiplatelets and anticoagulants exhibit their effect by blocking the activation pathways of platelets and the coagulation cascade, respectively. Clinical trials have demonstrated the safety and efficacy of antiplatelets for noncardioembolic stroke prevention, while anticoagulants are more often used for cardioembolic stroke prevention. Commonly used antiplatelets include aspirin, clopidogrel, and aggrenox (aspirin plus extended-release dipyridamole). Furthermore, commonly used anticoagulants include warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban. Each of these drugs has a unique mechanism of action, and they share some common adverse events such as gastrointestinal bleeding and intracranial hemorrhage in more serious cases. Consequently, physicians should carefully assess the benefits and risks of using different antiplatelet or anticoagulant therapies when managing patients with previous ischemic stroke or TIA. This review discuses the published literature on major clinical trials assessing the efficacy of different antiplatelet and anticoagulant drugs under varying circumstances and the subsequent guidelines that have been developed by the American Heart Association/American Stroke Association. Additionally, the role of imaging in stroke prevention is discussed.

Comparisons between Garcia, Modo, and Longa rodent stroke scales: Optimizing resource allocation in rat models of focal middle cerebral artery occlusion.

The use of rodent stroke models allow for the understanding of stroke pathophysiology. There is currently no gold standard neurological assessment to measure deficits and recovery from stroke in rodent models. Agreement on a universal preclinical stroke scale allows for comparison of the outcomes among conducted studies. The present study aimed to compare three routinely used neurological assessments in rodent studies (i.e., Garcia, Modo, and Longa) to determine which is most effective for accurately and consistently quantifying neurological deficits in the context of focal middle cerebral artery occlusion (MCAo) in rats. Focal MCAo was induced in 22 male Wistar rats using a novel transfemoral approach. Rodents were assessed for neurological deficit pre-injury as well as 3 and 24h post-injury. Data was analyzed to determine Pearson correlation coefficients in addition to McNemar's χ(2) values between each pair of neurological assessments. All three stroke scales, Garcia, Modo, and Longa, showed statistically significant changes between the baseline and the 3-hour neurological assessments. A trend towards neurological recovery was observed in all three stroke scales between the 3 and 24-hour endpoints. The three scales were highly correlated with each other, with Garcia and Modo having the strongest correlation. Of the three pairwise analyses, the comparison between the Garcia and Longa tests demonstrated the highest McNemar's χ(2) value, indicating least marginal homogeneity between these two tests. The combination of high correlation between Garcia and Modo tests along with greatest marginal heterogeneity observed between the Garcia and Longa test lead us to recommend the use of Garcia and Longa neurological scales when researchers are hoping to capture the broadest range of neurological factors using only two stroke scales.