Efficacy of sonothrombolysis in a rat model of embolic ischemic stroke

The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol (n = 7 died early). Four different groups (no treatment n = 6; full dose rt-PA treatment only [10 mg/kg per body weight] n = 14, half dose rt-PA treatment plus ultrasound n = 10, and full dose rt-PA treatment plus ultrasound n = 17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81+/-72 mm(3); P< 0.05) in comparison to untreated rats (253+/-159 mm(3); P < 0.05) as well as in comparison to rats treated with full dose rt-PA only (167+/-91 mm(3); P < 0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.     

Defects in regulation of apoptosis in caspase-2-deficient mice

During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.     

Do Treatment Plans Matter? Moving From Recommendations to Action

We investigated whether a service-planning document outlining recommendations for what providers should address in treatment (i.e., targets) and the associated clinical techniques they should employ (i.e., practices) influenced the targets and practices that providers reported actually implementing during the subsequent treatment episode. Participants included 94 youths ages 4 to 17 (M = 13.57, SD = 3.59) who received community-based mental health services from the Hawai'i Child and Adolescent Mental Health Division. Data on targets and practices were compared across initial Mental Health Treatment Plans and Monthly Treatment and Progress Summaries. Data were analyzed using two-level, generalized mixed effects models with two-way cross-classification or linear mixed effects models. Providers were more likely to report the use of targets and practices in treatment if they were included within the treatment plan. In addition, the more closely targets addressed during treatment followed the recommended targets from the treatment plan, the more closely implemented practices followed the recommended practices listed in the treatment plan. Furthermore, as providers shifted their focus to different targets, a shift in their use of practices was also evident over time. Last, practices for which there is demonstrated efficacy for particular targets were more likely to be used. Service planning documents appear to help organize care; however, results also suggest possible limitations to the current system. These findings highlight potential areas for improvement in planning and care delivery.     

Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation.

We investigated the effects of unilateral electrical trigeminal ganglion stimulation (0.1 or 1.0 mA, 5 Hz, 5 ms, 5 min) on the morphology of blood vessels within the rat dura mater and tongue using light and transmission electron microscopy. Stimulation at both intensities caused changes which were confined to the ipsilateral post-capillary venules except in the tongue where arterioles were affected as well. Changes were more marked after 1.0 mA. Dramatic increases in the numbers of endothelial pinocytotic vesicles were found along the luminal and abluminal surfaces ipsilateral to the stimulation. Tight junctions remained largely intact, except that injected ferritin particles were occasionally trapped inside these junctions. Cytoplasmic microvilli and endothelial blebs were sometimes present as well. Approximately 80% of the examined dural post-capillary venules showed one or more of these endothelial changes. Horseradish peroxidase injected intravenously 5 min prior to stimulation was detected in the extracellular space surrounding dural blood vessels and within pinocytotic vesicles. Ferritin injected similarly, was also localized in post-capillary venule walls, interstitial spaces, intraendothelial vesicles and in vacuoles. Platelet accumulation and aggregation were present in approximately 10% of post-capillary venules in dura and tongue. These changes were associated with mast cell secretion, but neither vascular nor mast cell activation was observed in adult rats in whom C-fibers were destroyed during the neonatal period with capsaicin. The present observations provide morphological evidence which supports findings from previously reported albumin tracer studies suggesting enhanced transport and endothelial activation following electrical stimulation of small caliber afferent fibers.