Post-stroke Conditions Research Articles

Abstract 3133: Impact of Post-stroke Isolation on Stroke Outcome

Background: Psychosocial factors are increasingly accepted as critical factors in post-stroke recovery, mortality and morbidity. Although, emerging data from clinical and population based studies support the role of social support in improved functional recovery and reducing the risk of mortality, to date no experimental studies have investigated such effects in post-stroke animal models. The aim of this study is to investigate for the impact of post stroke housing and the effects of long-term social isolation and pair housing with either a healthy or a stroked partner, and explored for the mechanisms. Methods: Male mice (20-25g; C57BL/6N, Charles River Labs), all initially pair housed, were subjected to right middle cerebral artery occlusion (MCAO - 60min) and then randomly assigned to a specific housing condition - isolated, paired with a stroke partner or paired with a healthy partner. Infarct size was quantified with TTC 72h after stroke (n=8/grp). We then investigated the effects of housing on long-term functional recovery using corner test, cylinder test, forced swim test (FST) and tail suspension test (TST). We further explored the mechanisms underlying the improved behavioral recovery by injecting BrDU 150mg/kg/day i.p. for 5 days starting from day 3 post-stroke (n=8/grp), and assessing changes in BDNF levels by western-blot analysis (n=4/grp). Data were expressed as mean±sem. Two-way ANOVA was performed and P value < .05 was set for statistical significance. Results: Post-stroke housing conditions can significantly impact infarct size; we observed that mice isolated after stroke had increased infarct volume compared to pair housed mice in all three brain regions (Cortex: 63.2±2.5 vs 40.0±6.2; p<0.01); (Striatum: 86.6±2.2 vs 67.7±2.9; p<0.01); (Total: 60.9±1.3 vs 32.6±4.3; p<0.01). Although post-stroke housing with healthy vs a stroked partner did not influenced infarct size (p>0.05), animals pair housed with healthy partner showed a significantly improved functional recovery by as early as day 15 in the cylinder and corner tests (p<0.05). Increased mobility was observed in FST and TST in PH mice compared to SI mice at day 90 (p<0.05). Consistently, housing with a healthy partner increased BrDU positive cells (p<0.05) and enhanced BDNF expression compared to other cohorts (SI 1±0.1; PH with stroke partner 1.9±0.2; PH with healthy partner 2.6±0.1; n=4/grp), no changes were seen in sham mice. Conclusions: Post-stroke housing has an important impact on stroke outcome; isolation has a detrimental effect on infarct size compared to pair housed cohorts. Interestingly, independent of infarct size, housing with a healthy partner hastened recovery compared to those stroke mice housed with partner that had also been subjected to stroke. Molecular analysis indicates the involvement of BDNF and neurogenesis may be important regulators of post-stroke housing induced functional recovery.

Quantum Dot Labeling of Butyrylcholinesterase Maintains Substrate and Inhibitor Interactions and Cell Adherence Features

Butyrylcholinesterase (BChE) is the major acetylcholine hydrolyzing enzyme in peripheral mammalian systems. It can either reside in the circulation or adhere to cells and tissues and protect them from anticholinesterases, including insecticides and poisonous nerve gases. In humans, impaired cholinesterase functioning is causally involved in many pathologies, including Alzheimer's and Parkinson's diseases, trait anxiety, and post stroke conditions. Recombinant cholinesterases have been developed for therapeutic use; therefore, it is important to follow their in vivo path, location, and interactions. Traditional labeling methods, such as fluorescent dyes and proteins, generally suffer from sensitivity to environmental conditions, from proximity to different molecules or special enzymes which can alter them, and from relatively fast photobleaching. In contrast, emerging development in synthesis and surface engineering of semiconductor nanocrystals enable their use to detect and follow molecules in biological milieus at high sensitivity and in real time. Therefore, we developed a platform for conjugating highly purified recombinant human BChE dimers (rhBChE) to CdSe/CdZnS quantum dots (QDs). We report the development and characterization of highly fluorescent aqueous soluble QD-rhBChE conjugates, present maintenance of hydrolytic activity, inhibitor sensitivity, and adherence to the membrane of cultured live cells of these conjugates, and outline their advantageous features for diverse biological applications.

Hyperactive and anxious phenotype following brief ischemic episodes in mice

Post-stroke emotional and behavioural abnormalities include a wide range of emotional and cognitive disturbances and have significant impact on long-term outcome. In animals models of stroke however there is little evidence of possible behavioural correlates of such post-stroke neuropsychiatric conditions. Here, we tested whether mild focal brain ischemia induces long-term behavioural changes and neuropsychiatric outcome in mice. 129/SV wild-type mice were anesthetized with isofluorane and subjected to 30 min filamentous occlusion of the left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 10 animals per group). Eight weeks after MCAo, animals were consecutively subjected to three behavioural tests, i.e. (1) spontaneous locomotor activity testing (day 56), (2) the elevated plus-maze (day 63 and (3) the modified Porsolt forced swim test (on day 70). We present evidence that mild cerebral ischemia is associated with increased spontaneous locomotor activity (right MCAo > left MCAo > sham) and with post-stroke anxiety (left MCA > right MCAo > sham), but we obtained no evidence of a post-stroke depressive phenotype. Noradrenaline levels were significantly increased by 30 – 45% in the ischemic striatum and significantly correlated with locomotor activity (r = 0.48) while the levels of dopamine and homovanillinic acid were decreased compared to sham operated animals. The ischemic lesion was confined to the ipsilateral striatum and scattered neuronal death was observed in a number of remote brain regions. In conclusion, brief ischemic episodes induce an hyperactive, anxious but not depressive phenotype in mice, that may relate to left versus right hemispheric lesion location, specific alterations in brain monoamine levels and selective neurodegeneration.

Relationships among Three Clinical Measures of Muscle Tone in Shoulders and Wrists of Patients with Poststroke Conditions

The association among three measures of muscle hypertonus were studied in shoulder internal rotation and wrist flexion on 49 poststroke subjects. Measures used were resting joint position, resistance to passive movement, and the angle at which the resistance appeared. Subjects were tested while seated with the affected arm supported and free to move in an adapted suspension armsling. Five of the six pairs of measurements (three at each joint) showed statistically significant associations with correlations between -.922 and .668 (p < .05) though the conditions under which they appeared differed. Results suggest that shoulder resting joint position and shoulder resistance to passive movement might be used interchangeably when muscle tone is measured only or first at the shoulder joint. Patterns of correlations suggest that factors underlying resting joint position differ fundamentally from those underlying resistance to passive movement and the angle at which resistance appears.