Effect of Extracellular Vesicles on Neural Functional Recovery and Immunologic Suppression after Rat Cerebral Apoplexy.

BACKGROUND: Previous studies have demonstrated that mesenchymal stem cells (MSCs) can promote the recovery of neural function after cerebral apoplexy by secreting multiple cytokines. In addition, cell factor-derived extracellular vesicles play an important role in recovery of neural function. The aim of this study was to determine the effect of extracellular vesicles on neural functional recovery and brain tissue remodeling after cerebral apoplexy in a rat model. METHODS: The rat models with local ischemic stroke was established and three random groups were created. In groups A and B, human bone marrow-derived MSCs and MSC-derived extracellular vesicles were transplanted into rats. In the control group (group C), only normal saline was injected. Then, we evaluated motor coordination ability, pathologic changes of the brain, immune responses in the central and peripheral nervous systems, regeneration of blood vessels, and nervous tissue in 4 weeks after cerebral apoplexy. RESULTS: Obvious regeneration of blood vessels and nervous tissues were identified in groups A and B. There was no significant difference with respect to coordination between groups A and B, but coordination in groups A and B was significantly better than the control group. Immunohistochemical staining of brain tissue showed that extracellular vesicles exerted no effect on infiltration of immune cells in the central nervous system. Weakened immune suppression was noted 1 week after cerebral apoplexy, which provided a favorable environment for remodeling of brain tissue. CONCLUSION: MSC-derived extracellular vesicles accelerated neural functional recovery after cerebral apoplexy. The weakened immune suppression was beneficial to remodeling of brain tissue.

CD163/Hemoglobin Oxygenase-1 Pathway Regulates Inflammation in Hematoma Surrounding Tissues after Intracerebral Hemorrhage.

BACKGROUND: The aim of the present study was to investigate changes in the expression of CD163 and hemoglobin oxygenase-1 (HO-1) in brain tissue surrounding hematomas after intracerebral hemorrhage (ICH), and correlations with other factors. MATERIALS AND METHODS: Brain tissues in the close surrounding of ICH hematomas (n = 27, ICH group) were collected at 6 hours or less, 6-24 hours, 24-72 hours, and more than 72 hours after bleeding onset, and more distant tissues (n = 12, control group) were histologically analyzed with hematoxylin and eosin staining and transmission electron microscopy. Interleukin (IL)-1, IL-10, and tumor necrosis factor-alpha, as well as the expression of CD163 and HO-1, were assessed using immunochemistry, Western blotting, and reverse transcription-polymerase chain reaction. Apoptosis rates were determined with terminal deoxynucleotidyl transferase dUTP nick end labeling assays. RESULTS: The expressions of the inflammatory cytokines IL-1 and tumor necrosis factor-alpha were increased at 6-24 hours (P <.05), reached a peak at 24-72 hours (P <.001 and P <.01), at which time histopathological changes became most obvious and apoptosis rates were highest, but diminished for more than 72 hours after ICH onset. The anti-inflammatory cytokine IL-10 peaked at 6-24 hours (P < .01) after ICH onset but dropped in the following periods to lower levels than the control (P <.05). CD163 and HO-1 expressions gradually increased from 6 to 24 hours to peaks at more than 72 hours after ICH onset (P <.001). CONCLUSION: The highest inflammation level in tissues surrounding ICH hematomas occurred 2-3 days after bleeding onset, but was accompanied by an anti-inflammatory factor IL-10 expression enhancement. In the period of more than 72 hours after ICH onset, CD163 and HO-1 expressions reached peaks and inflammatory cytokine expressions dropped.

Correlations between age, biomedical variables, and cognition in patients with schizophrenia.

OBJECTIVE: To illustrate the influence of clinical variables on cognition performance in patients with schizophrenia (SCZ). METHODS: Using the 66nao Brain Training device (a novel measurement tool), the cognitive performance of 99 patients with SCZ was evaluated. Patients were diagnosed by the ICD-10 diagnostic criteria for SCZ, and their age were 16-68 years old. Furthermore, we explored the relationship between age, biomedical variables and specific cognitive domains in patients with SCZ. Patients were divided into two groups: various of cognitive domains impairment group and non-impairment group according to the norm scores. All data were analyzed using RStudio Version 1.0.44 (RStudio, Inc.). RESULTS: Patients with SCZ had obvious cognitive impairment in total and five subdomains of cognitive function. We found that 1) SCZ patients with impaired cognitive total score experienced significant older age and longer illness duration compared with those with normal cognitive total score. 2) SCZ patients with impaired memory experienced significant older age compared with those with normal memory. 3) SCZ patients with impaired attention showed significant lower serum triglyceride (TG) level compared with those with normal attention. 4) SCZ patients with impaired flexibility performed significant longer illness duration compared with those with normal flexibility. 5) SCZ patients with impaired cognitive agility performed significant older age, longer duration, and higher systolic blood pressure (SBP) compared with those with normal cognitive agility. 6) The age, illness duration and SBP in patients with impaired time perception were marginally different from those of subjects with normal time perception. CONCLUSION: There are five dimensions (memory, attention, flexibility, cognitive agility, and time perception) of cognitive dysfunction in SCZ patients. Age, illness duration, TG, and SBP might play vital roles in various subdomains of the cognitive deficits respectively in patients with SCZ.

Sympathetic skin response and heart rate variability in predicting autonomic disorders in patients with Parkinson disease.

The purpose of this study was to evaluate sympathetic skin response (SSR) and heart rate variability (HRV) in determining autonomic nervous system (ANS) involvement in patients with Parkinson disease (PD). Forty-eight idiopathic PD patients and 30 healthy controls participated in this study. SSR, HRV, Unified Parkinson's Disease Rating Scale (UPDRS) III, the Scales for outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Hoehn and Yahr (H&Y) scale were evaluated. Absent lower limb SSR was determined unilaterally in 2, bilaterally in 1 of 3 advanced PD patients; there was significant difference between PD and control groups in terms of the SSR (P < 0.01), significant prolonged SSR latencies and decreased SSR amplitudes from bilateral hands and feet. Significant difference was noted in HRV between PD and control groups except for root mean square of successive differences (rMSSD) and high-frequency (HF) power (P < 0.05). There was a significant different correlation between the parameters of SSR and the SCOPA-AUT, and between the parameters (except HF power) of HRV and the SCOPA-AUT. Some parameters of SSR were relevantly associated with HRV. The right hand SSR amplitude correlated positively with the (SD) of all R-R interval, total spectral power, very low frequency. The right foot amplitude correlated positively with total spectral power. Both SSR and HRV parameters are sensitive in determining ANS dysfunction not only in late but also in the early stage of PD, which can be used for early detection of autonomic dysfunction in patients with PD and have the potential to serve as electrophysiological markers of dysautonomia of PD.

A Case Report of Locked-in Syndrome Due to Bilateral Vertebral Artery Dissection After Cervical Spine Manipulation Treated by Arterial Embolectomy.

Cervical spine manipulation (CSM) is a commonly spinal manipulative therapies for the relief of cervical spine-related conditions worldwide, but its use remains controversial. CSM may carry the potential for serious neurovascular complications, primarily due to vertebral artery dissection (VAD) and subsequent vertebrobasilar stroke. Here, we reported a rare case of locked-in syndrome (LIS) due to bilaterial VAD after CSM treated by arterial embolectomy.A 36-year-old right-handed man was admitted to our hospital with numbness and weakness of limbs after treating with CSM for neck for half an hour. Gradually, although the patient remained conscious, he could not speak but could communicate with the surrounding by blinking or moving his eyes, and turned to complete quadriplegia, complete facial and bulbar palsy, dyspnea at 4 hours after admission. He was diagnosed with LIS. Then, the patient was received cervical and brain computed tomography angiography that showed bilateral VAD. Aortocranial digital subtraction angiography showed vertebrobasilar thrombosis, blocking left vertebral artery, and stenosis of right vertebral artery. The patient was treated by using emergency arterial embolectomy and followed by antiplatelet therapy and supportive therapy in the intensive care unit and a general ward. Twenty-seven days later, the patient's physical function gradually improved and discharged but still left neurological deficit with muscle strength grade 3/5 and hyperreflexia of limbs.Our findings suggested that CSM might have potential severe side-effect like LIS due to bilaterial VAD, and arterial embolectomy is an important treatment choice. The practitioner must be aware of this complication and should give the patients informed consent to CSM, although not all stroke cases temporally related to SCM have pre-existing craniocervical artery dissection.

[The effects of chronic hypoxic hypercapnia on the TLR4 and NFkappaB in hippocampus neuron in rats].

AIM: To study the expression and effect of TLR4 and NFkappaB protein in hippocampus neuron in rats exposed to chronic hypoxic hypercapnia. METHODS: The disorder of learning-memory in pulmonary hypertension rat model was reproduced by chronic hypoxic hypercapnia. Thirty rats were randomly divided into three groups: normal control group, hypoxic hypercapnia 2-week and 4-week group. The number of apoptosis neurons in hippocampus CA1/3 was counted by TUNEL method. Activity of TLR4 and NFkappaB in hippocampus CA1/3 was detected by using SP immunocytochemical technique. RESULTS: The expression of TLR4 protein in hippocampus CA1/3 in group 2HH( CA1: 0.1275 +/- 0.0242, CA3: 0.1156 +/- 0.0376) and 4HH (CA1: 0.1522 +/- 0.0187, CA3: 0.1427 +/- 0.0453) were significantly higher than those in the NC group (P < 0.05, P < 0.01). The positive expression of NFkappaB were showed in cell nucleus in group 2HH (CA1: 0.1326 +/- 0.0324, CA3: 0.1301 +/- 0.0112) and group 4HH (CA1: 0.1612 +/- 0.0428, CA3: 0.1578 +/- 0.0365), and significantly higher than those in the NC group (P < 0.05, P < 0.01). The apoptosis of neural cells in hippocampus CA1/3 gradually increased with the time of exposure, and reached peak at 4 weeks (P < 0.01 vs NC group). CONCLUSION: The activation of TLR4 and NFkappaB may play an important role in the apoptosis of hippocampus neural cells in rat exposed to chronic hypoxic hypercapnia.

[Effects of chronic hypoxic hypercapnia on spatial learning-memory and expression of NMDAR1 in rats].

AIM: To explore the effect of chronic hypoxic hypercapnia on learning-memory and the possible mechanisms involved. METHODS: Fifty-eight male SD rats were randomly divided into three groups: Normal control group (NC, n=18), 2-week (2HH, n=18), and 4-week hypoxic hypercapnia (4HH, n=20) group. The rats, spatial learning-memory tasks were assessed by the Morris water maze. The expression of NMDAR1mRNA was determined by hybridization in situ. RESULTS: Compared with NC group, rats exposed to chronic hypoxic hypercapnia displayed significant impairment in their performance assessed by two measures: mean escape latencies (2HH: 38.59 +/- 8.35 s, 4HH: 60.59 +/- 17.28 s) and swim path distances(2HH: 9893.45 +/- 1958.16 mm, 4HH: 18077.57 +/- 6878.85 mm). The expression level of NMDAR1mRNA in the hippocampus and cortex were lower than those in the NC group, especially, the NMDAR1mRNA expression of hippocampus CA1 in 4HH decreased by 21.4% (P < 0.01). CONCLUSION: Chronic hypoxic hypercapnia could impair the rat spatial learning-memory and the decrease in expression of NMDAR1mRNA might be involved in.