Breaking up sitting time after stroke (BUST-stroke).

OBJECTIVES: People with stroke sit for long periods each day, which may compromise blood glucose control and increase risk of recurrent stroke. Studies in other populations have found regular activity breaks have a significant immediate (within-day) positive effect on glucose metabolism. We examined the effects of breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity in people with stroke on post-prandial plasma glucose and insulin. METHODS: Randomized within-participant crossover trial. We included people between 3 months and 10 years post-stroke, ambulant with minimal assistance and not taking diabetic medication other than metformin. The three experimental conditions (completed in random order) were: sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Meals were standardized and bloods were collected half- to one-hourly via an intravenous cannula. RESULTS: A total of 19 participants (9 female, mean [SD] age 68.2 [10.2]) completed the trial. The majority ( n = 12, 63%) had mild stroke symptoms (National Institutes of Stroke Scale score 0-13). There was no significant effect of experimental condition on glucose (mean [SD] positive incremental area [+iAUC] mmol·L·h-1 under the curve during sitting 42.3 [29.5], standing 47.4 [23.1], walking 44.6 [26.5], p = 0.563) or insulin (mean + iAUC pmol·L·h-1 sitting 14,161 [7,560], standing 14,043 [8,312], walking 14,008 [8,269], p = 0.987). CONCLUSION: Frequent, short bouts of light-intensity physical activity did not have a significant effect on post-prandial plasma glucose and insulin in this sample of people with stroke. Further studies are needed to identify strategies that improve inactivity-related glucose metabolism after stroke.

Frequent, short bouts of light-intensity exercises while standing decreases systolic blood pressure: Breaking Up Sitting Time after Stroke (BUST-Stroke) trial.

BACKGROUND: Stroke survivors sit for long periods each day. Uninterrupted sitting is associated with increased risk of cardiovascular disease. Breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity has an immediate positive effect on blood pressure and plasma clotting factors in healthy, overweight, and type 2 diabetic populations. AIM: We examined the effect of frequent, short bouts of light-intensity physical activity on blood pressure and plasma fibrinogen in stroke survivors. METHODS: Prespecified secondary analyses from a three-armed randomized, within-participant, crossover trial. Participants were 19 stroke survivors (nine female, aged 68 years old, 90% able to walk independently). The experimental conditions were sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Blood pressure was measured every 30 min over 8 h and plasma fibrinogen at the beginning, middle, and end of each day. Intention-to-treat analyses were performed using linear mixed models including fixed effects for condition, period, and order, and a random intercept for participant to account for repeated measures and missing data. RESULTS: Sitting with 3 min bouts of light-intensity exercise while standing every 30 min decreased systolic blood pressure by 3.5 mmHg (95% CI 1.7-5.4) compared with sitting for 8 h uninterrupted. For participants not taking antihypertensive medications, sitting with 3 min of walking every 30 min decreased systolic blood pressure by 5.0 mmHg (95% CI -7.9 to 2.0) and sitting with 3 min bouts light-intensity exercise while standing every 30 min decreased systolic blood pressure by 4.2 mmHg (95% CI -7.2 to -1.3) compared with sitting for 8 h uninterrupted. There was no effect of condition on diastolic blood pressure (p = 0.45) or plasma fibrinogen levels (p = 0.91). CONCLUSION: Frequent, short bouts of light-intensity physical activity decreases systolic blood pressure in stroke survivors. However, before translation into clinical practice, the optimal duration and timing of physical activity bouts needs to be determined. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry http://www.anzctr.org.au ANZTR12615001189516.

Tyrosine hydroxylase regulation in adult rat striatum following short-term neonatal exposure to manganese.

Manganese (Mn) is an essential trace element required for a range of physiological processes, but Mn can also be neurotoxic especially during development. Excess levels of Mn accumulate preferentially in the striatum and can induce a syndrome called manganism, characterized by an initial stage of psychiatric disorder followed by motor impairment. In the present study, we investigated the effects of Mn exposure on the developing dopaminergic system, specifically tyrosine hydroxylase (TH) protein and phosphorylation levels in the striatum of rats. Neonatal rats were exposed to Mn intraperitoneally (ip) from post-natal day 8 up to day 12 (PND8-12). Striatal tissue was analysed on PND14 or PND70, to detect either short-term or long-term effects induced by Mn exposure. There was a dose dependent increase in TH protein levels in the striatum at PND14, reaching significance at 20 mg kg(-1) Mn, and this correlated with an increase in TH phosphorylation at serines 40, 31 and 19. However, in the striatum at PND70, a time by which Mn levels were no longer elevated, there was a dose dependent decrease in TH protein levels, reaching significance at 20 mg kg(-1) Mn, and this correlated with TH phosphorylation at Ser40 and Ser19. There was however a significant increase in phosphorylation of TH at serine 31 at 20 mg kg(-1) Mn, which did not correlate with TH protein levels. Taken together our findings suggest that neonatal Mn exposure can have both short-term and long-term effects on the regulation of TH in the striatal dopaminergic system.

Tyrosine hydroxylase phosphorylation in catecholaminergic brain regions: a marker of activation following acute hypotension and glucoprivation.

The expression of c-Fos defines brain regions activated by the stressors hypotension and glucoprivation however, whether this identifies all brain sites involved is unknown. Furthermore, the neurochemicals that delineate these regions, or are utilized in them when responding to these stressors remain undefined. Conscious rats were subjected to hypotension, glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH and/or, the expression of c-Fos were determined, in up to ten brain regions simultaneously that contain catecholaminergic cell bodies and/or terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Glucoprivation evoked phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens whereas hypotension evoked changes A1, caudal C1, rostral C1, A6, A8/9, A10 and medial prefrontal cortex 30 min post stimulus whereas few changes were evident at 60 min. Although increases in pSer19, indicative of depolarization, were seen in sites where c-Fos was evoked, phosphorylation changes were a sensitive measure of activation in A8/9 and A10 regions that did not express c-Fos and in the prefrontal cortex that contains only catecholaminergic terminals. Specific patterns of serine residue phosphorylation were detected, dependent upon the stimulus and brain region, suggesting activation of distinct signaling cascades. Hypotension evoked a reduction in phosphorylation in A1 suggestive of reduced kinase activity. TH activity was increased, indicating synthesis of TH, in regions where pSer31 alone was increased (prefrontal cortex) or in conjunction with pSer40 (caudal C1). Thus, changes in phosphorylation of serine residues in TH provide a highly sensitive measure of activity, cellular signaling and catecholamine utilization in catecholaminergic brain regions, in the short term, in response to hypotension and glucoprivation.