The long-term effects of intermittent theta burst stimulation on Alzheimer's disease-type pathologies in APP/PS1 mice.

Intermittent theta burst stimulation (iTBS), an emerging and highly efficient paradigm of repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to mitigate cognitive impairment in Alzheimer's disease. Previous clinical studies have shown that the cognitive improvement of iTBS could last several weeks after treatment. Nonetheless, it is largely uncertain how the long-term effects of iTBS treatment are sustained. To investigate whether iTBS has a long-term effect on AD-type pathologies, 6-month-old APP/PS1 mice are administrated with 30 consecutive days of iTBS treatment. After a 2-month interval, morphological alterations in the brain are examined by immunohistochemistry and immunofluorescence staining, while levels of associated proteins are assessed by Western blot at the age of 9 months. We find that iTBS treatment significantly diminishes Aß burden in the cerebral cortex and hippocampus of APP/PS1 mice. Moreover, we observe that iTBS treatment inhibits the expression of BACE1 and elevates the level of IDE, suggesting that the reduction of Aß load could be attributed to the inhibition of Aß production and facilitation of Aß degradation. Furthermore, iTBS treatment attenuates neuroinflammation, neuronal apoptosis, and synaptic loss in APP/PS1 mice. Collectively, these data indicate that 1 month of iTBS treatment ameliorates pathologies in the brain of AD mice for at least 2 months. We provide the novel evidence that iTBS may exert after-effects on AD-type pathologies via inhibition of Aß production and facilitation of Aß degradation.

Prevalence and clinical predictors of spasticity after intracerebral hemorrhage.

BACKGROUND: Spasticity is a common complication of intracerebral hemorrhage (ICH). However, no consensus exists on the relation between spasticity and initial clinical findings after ICH. METHODS: This retrospective study enrolled adult patients with a history of ICH between January 2012 and October 2020. The modified Ashworth scale was used to assess spasticity. A trained image analyst traced all ICH lesions. Multivariable logistic regression was used to examine the association between ICH lesion sites and spasticity. RESULTS: We finally analyzed 304 patients (mean age 54.86 ± 12.93 years; 72.04% men). The incidence of spasticity in patients with ICH was 30.92%. Higher National Institutes of Health stroke scale (NIHSS) scores were associated with an increased predicted probability for spasticity (odds ratio, OR = 1.153 [95% confidence interval, CI 1.093-1.216], p < .001). Logistic regression analysis revealed that lower age, higher NIHSS scores, and drinking were associated with an increased risk of moderate-to-severe spasticity (OR = 0.965 [95% CI 0.939-0.992], p = .013; OR = 1.068 [95% CI 1.008-1.130], p = .025; OR = 4.809 [95% CI 1.671-13.840], p = .004, respectively). However, smoking and ICH in the thalamus were associated with a reduced risk of moderate-to-severe spasticity (OR = 0.200 [95% CI 0.071-0.563], p = .002; OR = 0.405 [95% CI 0.140-1.174], p = .046, respectively) compared with ICH in the basal ganglia. CONCLUSIONS: Our results suggest that ICH lesion locations are at least partly associated with post-stroke spasticity rather than the latter simply being a physiological reaction to ICH itself. The predictors for spasticity after ICH were age, NIHSS scores, past medical history, and ICH lesion sites.

Prevalence and factors influencing the occurrence of spasticity in stroke patients: a retrospective study.

BACKGROUND: To describe the prevalence and clinical characteristics of stroke patients without spasticity, and simultaneously analyse the factors related to post-stroke non-spasticity. METHODS: In this retrospective study, information on patients hospitalized in the department of rehabilitation, Daping Hospital, over the past eight years was collected. Demographic information and clinical characteristics were statistically analysed. RESULTS: A total of 819 stroke patients with an average age of 61.66±13.72 years old were analysed, including 561 males (68.5%), and 258 females (31.5%). In this study, 201 (24.5%) patients developed spasticity, and 618 (75.5%) patients had no spasticity. Patients without spasticity were older than those with spasticity. Patients with ischemic stroke and mild functional impairment were also less likely to have spasticity. Post-stroke spasticity may be related to age [odd ratio (OR): 0.982; 95% CI:0.965 to 0.999; P = 0.042), hemorrhagic stroke (OR: 1.643; 95% CI: 1.029 to 2.626; P = 0.038), National Institute of Health Stroke Scale (NIHSS) Scores (OR: 1.132; 95% CI: 1.063 to 1.204; P = 0.000]. CONCLUSION: Most stroke patients do not have spasticity, especially the elderly, patients with ischemic stroke, and those with mild functional impairment, suggesting that not all upper motor nerve injuries lead to increased muscle tension. For young individuals, patients with hemorrhagic stroke, and those with moderate to severe functional impairment, close follow-up is necessary to identify the occurrence of spasticity early on and then formulate corresponding rehabilitation strategies for prompt intervention.

Repetitive Transcranial Magnetic Stimulation Decreases Serum Amyloid-ß and Increases Ectodomain of p75 Neurotrophin Receptor in Patients with Alzheimer's Disease.

BACKGROUND: This study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on serum levels of Amyloid-ß (Aß) as well as the ectodomain of p75 neurotrophin receptor (p75ECD) in patients with Alzheimer's disease (AD). METHODS: A total of 46 patients diagnosed with AD between June 1, 2020 and December 31, 2021 were randomized to undergo either 20 Hz rTMS treatment of the left dorsolateral prefrontal cortex (DLPFC) or sham procedure. Cognitive function and activity of daily living were evaluated. Neuropsychological tests and blood samples were gathered at baseline and at 2, 3, 4, and 6 weeks after rTMS therapy. RESULTS: There were no evident differences between rTMS group and sham group in serum Aß40, Aß42, total Aß, ApoE, and p75ECD standards at baseline (p > 0.05). Serum levels of Aß40, Aß42, as well as total Aß, were significantly lower in the rTMS group at 3, 4 and 6 weeks relative to the sham group (p < 0.05). Serum p75ECD levels in the rTMS group were significantly higher than those of the sham group at 3, 4 and 6 weeks (p < 0.05). Levels of serum Aß40 (r: -0.78, -0.83, -0.68, respectively), Aß42 (r: -0.76, -0.76, -0.61, respectively) and total Aß (r: -0.74, -0.81, -0.66, respectively) were negatively correlated with MoCA, MMSE and MBI scores, while serum p75ECD levels (r: 0.84, 0.90, 0.72, respectively) were positively correlated (p < 0.01). The level of serum Aß40 (r = 0.77), Aß42 (r = 0.69) as well as total Aß (r = 0.73) were positively correlated with ADAS-cog score, while p75ECD levels (r = -0.86) were negatively correlated (p < 0.01). CONCLUSIONS: The results of this study suggest that rTMS may decrease serum Aß levels and increase serum p75ECD levels in patients with AD, offering insight into a potential underpinning mechanism of rTMS.

Histological, enzymohistochemical and biomechanical observation of skeletal muscle injury in rabbits.

OBJECTIVE: To explore the pathophysiological and biomechanical features of skeletal muscular injury for providing a rational basis for its treatment, prevention and rehabilitation. METHODS: In 70 adult rabbits, the left tibialis anterior (TA) muscle was stretched to injury, while the right TA muscle served as control. Histological, enzymohistochemical and biomechanical changes were observed on days 0, 1, 2, 3, and 7 after injury. Cytochrome oxidase (CCO), acid phosphatase (ACP), ATPase, succinate dehydrogenase (SDH), malate dehydrogenase (MDH), NADH-diaphorase (NADHD), glutamatedehydrogenase (GDH), alpha-glycerophosphate dehydrogenase (alpha-GPD) and lactate dehydrogenase (LDH) were measured. The examined biomechanical parameters included maximal contractile force, ultimate load, length, energy absorption, tangent stiffness, and rupture site. RESULTS: Partial or complete rupture of TA muscle occurred near the muscle-tendon junction. There was an intense inflammatory reaction on day 1 and 2 after injury. Endomysium fibrosis and myotube formation were observed on day 3, and developed further on day 7. The activity of cell oxidases (CCO, ATPase, MDH, alpha-GPD, SDH, NADHD and GDH) showed a significant drop from day 0 to 2, and resumed with different levels on day 3. The increment of enzymatic activities continued on day 7 and the levels of NADHD and alpha-GPD reached to the levels of control muscle. Maximal contractile force was 70.17%+/-3.82% of controls immediately after injury, 54.82%+/-3.09% at 1 day, 66.41%+/-4.36% at 2 days, 78.39%+/-4.90% at 3 days and 93.64%+/-5.02% at 7 days. Ultimate load was 85.78%+/-7.54% of controls at the moment of injury, 61.44%+/-5.91% at 1 day, 49.17%+/-4.26% at 2 days, 64.43%+/-5.02% at 3 days, and 76.71%+/-6.46% at 7 days. CONCLUSIONS: Endomysium fibrosis and scar formation at the injured site are responsible for frequent recurrence of skeletal muscle injury. Recovery of tensile load slower than that of maximal contractile force may be another cause. Whether the injured muscle returns to normal exercise is mainly determined by the tensility on which the muscle-tendon can bear rather than the maximal contractile force.