The aim of this study was to investigate the neural plasticity in contralesional cortex and the effects of tongxinluo (TXL) in cerebral ischemic rats.
We used stroke-prone renovascular hypertensive (RHRSP) cerebral ischemia rat models to study the effect of TXL and the underlying mechanisms. We performed foot-fault and beam-walking tests to evaluate the motor function of rats after cortical infarction. Biotinylated dextran amine (BDA) was used to track axonal sprouting and neural connections.
TXL enhanced the recovery of motor function in cerebral infarction rats. TXL increased axonal sprouting in the peri-infarcted area but not in the corpus callosum, indicating in situ origination instead of crossing between cortical hemispheres through the corpus callosum. TXL promoted the sprouting of corticospinal axons into the denervated side of spinal gray matter. The synaptophysin (SYN)-positive intensity in the peri-infarcted area of TXL-treated group was greater than that in the vehicle group. We observed co-localization of SYN with BDA-positive fibers in the denervated spinal cord gray matter in the TXL group, suggesting that axonal remodeling and synaptic connections were promoted by TXL.
TXL may promote the recovery of neurological function by promoting the axonal remodeling and synapse formation of motor neuronal fibers after focal cortical infarction in hypertensive rats.
Deep brain stimulation (DBS) applied to the nucleus accumbens (NAc) alleviates the depressive symptoms of major depressive disorders. We investigated the mechanism of this effect by assessing gene expression and RNA methylation changes in the ventral tegmental area (VTA) following NAc-DBS in a chronic unpredictable mild stress (CUMS) mouse model of depression. Gene expression and N6-methyladenosine (m6A) levels in the VTA were measured in mice subjected to CUMS and then DBS, and transcriptome-wide m6A changes were profiled using immunoprecipitated methylated RNAs with microarrays, prior to gene ontology analysis. The expression levels of genes linked to neurotransmitter receptors, transporters, transcription factors, neuronal activities, synaptic functions, and mitogen-activated protein kinase and dopamine signaling were upregulated in the VTA upon NAc-DBS. Furthermore, m6A modifications included both hypermethylation and hypomethylation, and changes were positively correlated with the upregulation of some genes. Moreover, the effects of CUMS on gene expression and m6A-mRNA modification were reversed by DBS for some genes. Interestingly, while the expression of certain genes was not changed by DBS, long-term stimulation did alter their m6A modifications. NAc-DBS-induced modifications are correlated largely with upregulation but sometimes downregulation of genes in CUMS mice. Our findings improve the current understanding of the molecular mechanisms underlying DBS effects on depression.
Sudoku is a popular cognitively stimulating leisure-time activity. Many studies have been directed toward finding an algorithm to solve Sudoku, but the investigation of the neural substrates involved in Sudoku has been challenging.
Sudoku task was divided into two steps to understand the differential function of the prefrontal cortex (PFC) while applying heuristic rules. PFC activity was recorded at 16 optode locations using functional near infrared spectroscopy. Classical two-way analysis of variance as well as general linear model-based approach was used to analyze the data from 28 noise-free recordings obtained from right-handed participants.
Post hoc analysis showed a significant increase in oxyhemoglobin concentrations and decrease in deoxyhemoglobin concentrations at all 16 optode locations during step 1 (3 × 3 subgrids) and step 2 (easy level 9 × 9 Sudoku) when compared with the rest (p < 0.0001). Contrasting the step 2 – step 1 revealed that medial regions of PFC were preferentially activated.
Both the medial and lateral regions of PFC are activated during Sudoku task. However, the medial regions of PFC play a differential role, especially when we consider searching and selecting the heuristic rules. Thus, Sudoku may be used for cognitive remediation training in neuropsychiatric disorders involving PFC.
Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.
Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.
The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.
This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.
To investigate the effect and medical imaging of modified hemispherectomy on patients with infantile hemiparesis and medically refractory epilepsy.
Patients and methods
Forty-three patients with infantile hemiparesis and refractory epilepsy who underwent hemispherectomy were enrolled. The treatment effect and medical imaging were analyzed.
Anatomical hemispherectomy was successfully performed in all patients (100%). In all patients, the muscular tension decreased and the contracted limbs relaxed. In the pathological examination of the resected brain tissue, secondary cicatricial gyri with concomitant cortical dysplasia was present in 36 cases and polycerebellar gyrus malformation and porencephalia in the other 7 cases. Followed up for 7–15 years (mean 11.3), all patients were alive without a long-term sequela. Epilepsy was satisfactorily controlled, with complete seizure relief in 39 cases (91%) classified as Engel I and basic control in the other 4 (9%) defined as Engel II. The posthemispherectomy medical imaging demonstrated that the intracranial space on the operative side shrank, and the healthy cerebral hemisphere shifted markedly toward the hemispherectomy side, with expanded lateral ventricle on the healthy side and thickened skull and enlarged frontal sinus on the operative side. After 4–5 years, the intracranial space on the operative side disappeared in 75% of the patients, demonstrating enlarged cerebral peduncle on the healthy side.
Further modified hemispherectomy in patients with infantile hemiparesis and medically refractory epilepsy demonstrated markedly ameliorated effects on epilepsy control and the prevention of superficial cerebral hemosiderosis in the long-term follow-up.
Intracranial hemorrhage (ICH) causes high mortality and disability without effective treatment in the clinical setting. (−)-Epigallocatechin-3-gallate (EGCG) exerts an essential role in the central nervous system and offers a promising therapeutic agent for the treatment of oxidative damage-related diseases. MiR-137 can inhibit the oxidative stress and apoptosis to attenuate neuronal injury. However, the role of EGCG in regulating miR-137-3p and neuronal Parthanatos remains to be unclear. In the present study, we build the ICH mice model to investigate the antioxidant effects of EGCG via upregulating miR-137-3p and inhibiting neuronal Parthanatos. We revealed that EGCG upregulated miR-137-3p and inhibited neuronal Parthanatos, and promoted the functional recovery, alleviated ICH-induced brain injury, and reduced oxidative stress in mice following ICH. However, following the inhibition of miR-137-3p and activation of Parthanatos, EGCG was unable to exert neuroprotective roles. These combined results suggest that EGCG may upregulate miR-137-3p and inhibit neuronal Parthanatos to accelerate functional recovery in mice after ICH, laying the foundation for EGCG to be a novel strategy for the treatment of neuronal injuries related to Parthanatos.
Therapeutic management of pain in patients with complex regional pain syndrome (CRPS) is challenging. Repetitive transcranial magnetic stimulation (rTMS) has analgesic effects on several types of pain. However, its effect on CRPS has not been elucidated clearly. Therefore, we conducted a meta-analysis of the available clinical studies on rTMS treatment in patients with CRPS.
Materials and methods
A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases. We included studies published up to February 09, 2020, that fulfilled our inclusion and exclusion criteria. Data regarding measurement of pain using the visual analog scale before and after rTMS treatment were collected to perform the meta-analysis. The meta-analysis was performed using Comprehensive Meta-analysis Version 2.
A total of three studies (one randomized controlled trial and two prospective observational studies) involving 41 patients were included in this meta-analysis. No significant reduction in pain was observed immediately after one rTMS treatment session or immediately after the entire schedule of rTMS treatment sessions (5 or 10 sessions; P > 0.05). However, pain significantly reduced 1 week after the entire schedule of rTMS sessions (P < 0.001).
rTMS appears to have a functional analgesic effect in patients with CRPS.
Digital subtraction angiography (DSA) is considered the gold standard for cerebral vasculature observation and is increasingly applied among the elderly population. The aim of this study is to determine whether the use of a video-based education system can improve the image quality of percutaneous cerebral angiography.
This study is a single-blinded prospective cohort trial. One hundred and sixty patients (≥65 years old) were enrolled in this study. Eighty patients were provided with video-based education as intervention. Eighty age-matched controls only received regular education. The DSA image quality was assessed between control and intervention groups. It was rated by two readers on a 5-point scale, independently.
No differences were found between control and intervention groups in baseline characteristics (P > 0.05). The mean overall image quality was significantly higher in patients receiving video-based education than in controls (P < 0.05), and the same trends were found in the respective assessment of each artery (left and right carotid/vertebral artery; P < 0.05). Moreover, the operation time and radiation doses were quite comparable between the two groups (P > 0.05).
This study indicated that video-based education helps elderly patients to acquire improved DSA image quality. It encourages the application of this approach in practice.
We investigated injuries of the optic radiations (ORs) in patients with mild traumatic brain injury (TBI) by using diffusion tensor tractography (DTT).
Fifty-two consecutive patients who complained of visual problems showed abnormal visual evoked potential (VEP) latency but no abnormality on conventional brain MRI after mild TBI, and fifty normal control subjects were recruited for this study. Subjects’ ORs were reconstructed using DTT, and three DTT parameters (fractional anisotropy [FA], apparent diffusion coefficient [ADC], and tract volume) were measured for each OR.
Mean FA value and tract volume of the OR were significantly lower in the patient group than in the control group (p < 0.05). However, there was no significant difference in the ADC values of the OR between the patient and control groups (p > 0.05). A weak negative correlation was detected between VEP latency and OR fiber number (r = 0.204, p < 0.05).
DTT revealed that OR injuries were not detected on the conventional brain MRI scans of patients who complained of visual problems and had abnormal VEP latency after mild TBI. Our results suggest that DTT would be a useful technique for detecting OR injury in patients with mild TBI.
Food consumption during the rest phase promotes circadian desynchrony, which is corrected with harmful physiological and mental disorders. Previously, we found that circadian desynchrony was involved in isoflurane-induced cognitive impairment. Here, we scheduled food access to modulate daily rhythm to examine its impact on isoflurane-induced cognitive impairments. Mice were randomly transferred to restricted feeding (RF) time groups: Control group (Zeitgeber time (ZT) 0–ZT24, ad libitum feeding), Day-Feeding group (ZT0–ZT12, misaligned feeding), and Night-Feeding group (ZT12–ZT24, aligned feeding). Then, some of them were subjected to 5 h of 1.3% isoflurane anaesthesia from ZT14 to ZT19 and were divided into the Control + Anes group, the Day-Feeding + Anes group, and the Night-Feeding + Anes group. Mini-Mitter was used to monitor the daily rhythm. Fear conditioning system was conducted to assess cognition of mice. We observed that the Night-Feeding group adapted to RF gradually, whereas the Day-Feeding group exhibited a disturbed daily rhythm. The Night-Feeding + Anes group exhibited a partially enhanced daily rhythm, whereas the Day-Feeding + Anes group exhibited sustained phase advances and diurnality score increase 7 days after isoflurane anaesthesia. Notably, in tests of hippocampus-dependent contextual memory, the Night-Feeding + Anes group demonstrated decreased deficits; the Day-Feeding + Anes group showed prolonged post-anaesthetic deficits 14 days after isoflurane anaesthesia. However, amygdala-dependent cued-fear conditioning post-anaesthesia was not altered by the RF schedule. In conclusion, we demonstrated that misaligned feeding disturbed the daily rhythm and led to persistent post-anaesthetic cognitive dysfunction. Aligned feeding enhanced the daily rhythm partially and improved post-anaesthetic cognitive dysfunction.