Corrigendum: Neuroprotective Effects of Celastrol on Transient Global Cerebral Ischemia Rats via Regulating HMGB1/NF-κB Signaling Pathway.

[This corrects the article DOI: 10.3389/fnins.2020.00847.].

Neuroprotective Effects of Celastrol on Transient Global Cerebral Ischemia Rats via Regulating HMGB1/NF-κB Signaling Pathway.

Cerebral ischemia is a major cause of brain dysfunction, neuroinflammation and oxidative stress have been implicated in the pathophysiological process of cerebral ischemia/reperfusion injury. Celastrol is a potent inhibitor of inflammation and oxidative stress that has little toxicity. The present study was designed to evaluate whether celastrol has neuroprotective effects through anti-inflammatory and antioxidant actions, and to elucidate the possible involved mechanisms in transient global cerebral ischemia reperfusion (tGCI/R) rats. Celastrol (1, 2, or 4 mg/kg) was administrated intraperitoneally immediately after reperfusion and the effect of celastrol on reverting spatial learning and memory impairment was determined by Morris water maze (MWM) task. Inflammatory response and oxidative stress, hippocampal neuronal damage and glial activation, and HMGB1/NF-κB signaling pathway proteins were also examined. Our results indicated that celastrol dose-dependently reduced hippocampal and serum concentration of pro-inflammatory markers (TNF-α, IL-1ß, and IL-6) and oxidative stress marker (MDA), whereas the anti-inflammatory marker IL-10 and antioxidant markers (GSH, SOD, and CAT) were increased significantly in celastrol treated tGCI/R rats. Celastrol alleviated apoptotic neuronal death, inhibited reactive glial activation and proliferation and improved ischemia-induced neurological deficits. Simultaneously, we found that mechanisms responsible for the neuroprotective effect of celastrol could be attributed to its anti-inflammatory and antioxidant actions via inhibiting HMGB1/NF-κB signaling pathway. These findings provide a proof of concept for the further validation that celastrol may be a superior candidate for the treatment of severe cerebral ischemic patients in clinical practice in the future.

Cdh1 overexpression improves emotion and cognitive-related behaviors via regulating hippocampal neuroplasticity in global cerebral ischemia rats.

Post-stroke survivors exhibited cognitive deficits and performed emotional impairment. However, the effect of global cerebral ischemia on standard behavioral measures of emotionality and underlying mechanism remain largely unknown. Our previous work identified that down-regulation of Cdh1 contributed to ischemic neuronal death in rat, thus we hypothesized that Cdh1 exerts a role in emotionality after cerebral ischemia, and we investigated the effect of Cdh1 overexpression on neurogenic behaviors and possible mechanisms in transient global cerebral ischemia reperfusion (tGCI/R) rats. A series of behavioral tests were used to evaluate emotion and cognitive related behaviors, and molecular biological techniques were employed to investigate hippocampal neuroplasticity. The results showed that tGCI/R rats displayed anxiety- and depression-like behaviors and a certain degree of cognitive impairment, and these abnormal behaviors accompanied with a loss of hippocampal synapses and dendritic spines, disruption of dendrite arborization and decline in the level of GAP-43, synaptophysin, synapsin and PSD-95. However, Cdh1 overexpression improved negative emotionality, ameliorated cognitive deficits, rescued hippocampal synapses loss, prevented dendritic network disorganization, and increased the level of synaptic-associated proteins after tGCI/R. Taken together, these findings suggest that Cdh1 overexpression exerts a neuroprotective effect by regulating hippocampal neuroplasticity thus improving negative emotionality and cognitive deficits after tGCI/R.

[Infrared radiation and magnetic field therapy ameliorates cartilage damage in rabbits with knee osteoarthritis].

OBJECTIVE: To evaluate the effect of infrared radiation and magnetic field therapy on cartilage damage in rabbits with knee osteoarthritis. METHODS: Knee osteoarthritis was induced in 24 adult New Zealand rabbits by prolonged fixation of the knee joint in extension for 6 weeks. The rabbits were subsequently randomized into control group (without treatment), infrared therapy group, magnetic field therapy group and the combined infrared and magnetic field therapy group. At the end of the first, second and third weeks of the therapy, respectively, 2 rabbits from each group were sacrificed to observe the general changes and histopathology of the condylar cartilage of the femur, and the findings were assessed using Mankin scores. RESULTS: Compared with other groups, the rabbits in the combined therapy group showed significantly milder cartilage damage (including injury of the cartilage surface and chondrocyte's proliferation and disarrangement) with significantly lower Mankin scores (P<0.05). No significant differences were found in the findings between the two groups with exclusive infrared or magnetic field therapy (P>0.1). CONCLUSION: Combined infrared and magnetic field therapy can effectively alleviate cartilage destruction, shortens the disease course and enhance the therapeutic effects in rabbits with knee osteoarthritis.

Regional variation in ICC distribution, pacemaking activity and neural responses in the longitudinal muscle of the murine stomach.

Intramuscular interstitial cells of Cajal (ICC-IM) play a critical role in enteric neural regulation of the circular muscle layer in the stomach, but no studies have been performed on the longitudinal layer. Kit immunohistochemistry was used to examine ICC-IM in the longitudinal muscle layer of the murine corpus and antrum, and it revealed marked heterogeneity in the distribution of ICC-IM in longitudinal muscles. In the corpus, ICC-IM were found along the greater curvature near the fundus. ICC-IM decreased in density in the circumferential axis toward the lesser curvature and in the longitudinal axis toward the antrum. ICC-IM were absent from the longitudinal layer of the antrum. Double labelling with markers for specific classes of enteric motor neurones revealed that cholinergic and nitrergic motor neurones formed close contacts with ICC-IM in the corpus but not in the antrum. Enteric nerve stimulation evoked prominent cholinergic excitatory and nitrergic inhibitory responses in longitudinal muscles of the corpus, but not in the antrum of wild-type animals. Cholinergic and nitrergic nerves were also present in W/W(V) mice, but functional innervation of the longitudinal muscle layer by these nerves in the corpus and antrum were absent. The data show that cholinergic and nitrergic neurotransmission only occurs in the gastric longitudinal layer in regions where ICC-IM are present. In regions, such as the corpus, where ICC-IM are common, robust neural responses are present, but the reduced density of ICC-IM near the lesser curvature and in the distal stomach leads to reduced neural regulation in these gastric regions.