scholarly journals Intracerebral transplantation of erythropoietin‐producing fibroblasts facilitates neurogenesis and functional recovery in an ischemic stroke model

2019 ◽  
Vol 9 (5) ◽  
pp. e01274 ◽  
Author(s):  
Pin‐Chun Chou ◽  
Yi‐Chieh Tsai ◽  
Shiu‐Jau Chen ◽  
Li‐Kai Tsai ◽  
Chung‐Liang Chien
PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10921
Author(s):  
Hongli Tang ◽  
Leiruo Wu ◽  
Xixi Chen ◽  
Huiting Li ◽  
Baojun Huang ◽  
...  

Background Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. Methods In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. Results The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1β, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. Conclusions These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.


2020 ◽  
Vol 60 (2) ◽  
pp. 83-93 ◽  
Author(s):  
Jumpei OSHITA ◽  
Takahito OKAZAKI ◽  
Takafumi MITSUHARA ◽  
Takeshi IMURA ◽  
Kei NAKAGAWA ◽  
...  

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Yoon Bum Lee ◽  
Seung Kuk Bae ◽  
Sung Suk Oh ◽  
Jong-ryul Choi

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.


2021 ◽  
pp. 251660852110112
Author(s):  
Kiran Buddharaju ◽  
Mahendra Javali ◽  
Anish Mehta ◽  
R Srinivasa ◽  
Purushottam Acharya

Background: Stroke is a major cause of neurological disability, which can be often predicted with serological markers. Glial-derived S100β protein is a potential biomarker for cerebral ischemia and may be helpful in predicting the severity, outcome, and recovery of stroke. Aim: This study aimed to study the role of S100β glial protein as a serological marker in predicting the severity of acute ischemic stroke (AIS), outcome, and functional recovery after 1 month. Methods: A hospital-based prospective case control study included 43 consecutive patients, >18 years old, who were admitted with acute middle cerebral artery (MCA) territory infarcts within 72 h of onset of neurological deficits. Control group comprised of 43 age-matched asymptomatic volunteers. Independent t-test and chi square test were used to compare the means and evaluate the association between protein level and various parameters. P ≤ .05 was statistically significant. Results: S100β protein level in AIS patients was significantly higher compared to controls ( P < .05). Elevated serum S100β protein level was found to be associated with larger infarct volumes, higher National Institute Health Stroke Scale scores, and higher modified Rankin Scale scores at admission ( P < .05). Patients with higher S100β protein levels at admission had poor recovery at 1 month compared to patients having normal S100β protein levels. Conclusion: S100β protein levels at admission after an acute MCA territory infarct may be used as a reliable serological tool in predicting the severity, outcome, and functional recovery in stroke.


2021 ◽  
Vol 13 (1) ◽  
pp. 46-58
Author(s):  
João Paulo Branco ◽  
Filipa Rocha ◽  
João Sargento-Freitas ◽  
Gustavo C. Santo ◽  
António Freire ◽  
...  

The objective of this study is to assess the impact of recanalization (spontaneous and therapeutic) on upper limb functioning and general patient functioning after stroke. This is a prospective, observational study of patients hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery (n = 98). Patients completed a comprehensive rehabilitation program and were followed-up for 24 weeks. The impact of recanalization on patient functioning was evaluated using the modified Rankin Scale (mRS) and Stroke Upper Limb Capacity Scale (SULCS). General and upper limb functioning improved markedly in the first three weeks after stroke. Age, gender, and National Institutes of Health Stroke Scale (NIHSS) score at admission were associated with general and upper limb functioning at 12 weeks. Successful recanalization was associated with better functioning. Among patients who underwent therapeutic recanalization, NIHSS scores ≥16.5 indicate lower general functioning at 12 weeks (sensibility = 72.4%; specificity = 78.6%) and NIHSS scores ≥13.5 indicate no hand functioning at 12 weeks (sensibility = 83.8%; specificity = 76.5%). Recanalization, either spontaneous or therapeutic, has a positive impact on patient functioning after acute ischemic stroke. Functional recovery occurs mostly within the first 12 weeks after stroke, with greater functional gains among patients with successful recanalization. Higher NIHSS scores at admission are associated with worse functional recovery.


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