Milk Fat Globule-Epidermal Growth Factor-8 Pretreatment Attenuates Apoptosis and Inflammation via the Integrin-ß3 Pathway after Surgical Brain Injury in Rats.

Iatrogenic brain injury inevitably occurs in neurosurgical operations, leading to brain edema, ischemia, intracranial hematoma, and other postoperative complications, eventually worsening neurological outcomes of patients. If apoptotic cells are not rapidly eliminated by phagocytic engulfment, they may communicate with surrounding cells to undergo secondary necrosis and releasing toxic signals. Recent studies have shown that milk fat globule-epidermal growth factor-8 (MFGE8), which promotes phagocytosis and inhibits inflammation, is an endogenous protective factor in response to brain infarction, Alzheimer's disease, subarachnoid hemorrhage, and prion disease. In the present study, we sought to investigate the different effects of both pretreated and posttreated recombinant milk fat globule-epidermal growth factor-8 (rhMFGE8) for the surgical brain injury (SBI) rat model and potential involvement of its receptor integrin ß3 for apoptosis and neuroinflammation after SBI. One hundred and sixty-seven male rats were employed in the preset study. Experiment 1 was performed to evaluate neurological scores and MFGE8, cleaved caspase-3 (CC3), and interleukine-1 beta (IL-1ß) levels at 3, 24, and 120 h after SBI. Experiment 2 was performed to evaluate the effects of rhMFGE8 pretreatment (10 min before SBI) and rhMFGE8 posttreatment (6 h after SBI) on brain edema at 24 and 72 h after SBI. Experiment 3 was performed to evaluate the potential anti-apoptotic and anti-inflammatory effects of rhMFGE8 pretreatment and posttreatment. Experiment 4 sought to investigate the involvement of the integrin-ß3 signal in the effects of MFGE8 pretreatment. Our data showed rhMFGE8 pretreatment alleviated neurological deficits and decreased brain water content and apoptotic cells in the SBI model, which exhibited neurological dysfunction, apoptosis, and inflammation. Meanwhile, MFGE8 siRNA, which inhibited endogenous MFGE8 expression, significantly increased IL-1ß, TUNEL positive cells, and CC3. Furthermore, knockdown of its receptor integrin ß3 by siRNA abolished the effects of rhMFGE8 in the SBI model. In conclusion, we found that rhMFGE8 pretreatment effectively alleviated neurological deficits and decreased brain water content and apoptotic cells in the SBI model through the MFGE8/integrin-ß3 pathway, and treatment time was an important factor in achieving curative effects. Therefore, MFGE8 pretreatment may serve as a promising therapeutic strategy for SBI patients.

[Methods and effects of injection of salvianolic acid B combined with triamcinolone acetonide in the treatment of oral submucous fibrosis].

PURPOSE: To introduce the methods of triamcinolone acetonide (TA) and salvianolic acid B(SA-B) intralesional injection in the treatment of oral submucous fibrosis and evaluate the treatment effects. METHODS: TA combined with SA-B were consecutively applied intralesionally 1 time weekly for 30 times. The technique of intralesional injection was that syringe needle be emptied into submucous tissues 1 cm posterior to the corner of oral cavity running from the front to retromolar area by pushing the injection, then the syringe needle retained to the original point and upward from the front to retromolar area by pushing the injection, finally the syringe needle returned to the starting point and downward from the front to retromolar area by pushing the injection. Mouth opening, the color change of the buccal mucosa and the increase of capillary vessels as determined by degree I-IV visual analog scale were evaluated at 12, 24, and 36 month. The data were analyzed with SPSS 21.0 software package. RESULTS: One hundred and fourteen subjects fulfilled the study without obvious adverse reactions. After treatment for 36 months , the net gain in mouth opening of the early stage group，middle stage group and advanced stage group was (12.0±1.2) mm, (14.5±2.4) mm and (15.5±1.5) mm, respectively. The response rate of color change of the buccal mucosa and the increase of capillary vessels in early stage group, middle stage group and advanced stage group after treatment for 36 months was 100%, 94.7% and 90.7%, respectively. CONCLUSIONS: Triamcinolone acetonide and salvianolic acid B intralesional injection is effective in the treatment of oral submucous fibrosis.

Optimal electroacupuncture frequency for maintaining astrocyte structural integrity in cerebral ischemia.

The astrocyte is a critical regulator of neuronal survival after ischemic brain injury. Electroacupuncture may be an effective therapy for cerebral ischemia, as electroacupuncture frequency can affect the structural integrity of astrocytes. In this study, a rat model of middle cerebral artery occlusion established using the modified thread embolism method was treated with electroacupuncture of the bilateral Quchi (LI11) and Zusanli (ST36) at 15, 30, and 100 Hz frequencies. Behavioral testing, immunohistochemistry and electron microscopy were used to explore the effect of these electroacupuncture frequencies used on maintaining the structural integrity of ischemic brain tissue. Compared with the model and 100 Hz electroacupuncture groups, the 15 and 30 Hz electroacupuncture groups displayed decreased neurological deficit scores, as evaluated by the "Longa" method, significantly increased glial fibrillary acidic protein expression, and alleviated ultrastructural damage of astrocytes at the edge of the infarct. Our experimental findings indicate that 15 and 30 Hz electroacupuncture intervention can favorably maintain the structural integrity of astrocytes and play a protective role in cerebral ischemic injury. Astrocyte structural integrity may be the mechanism underlying acupuncture production of ischemic tolerance.

[Effects of electroacupuncture at "Zusanli" (ST 36) and "Neiguan" (PC 6) on expression of GAP-43 in cerebral infarction rats].

OBJECTIVE: To observe the effect of electroacupuncture on the neural plasticity in rats with cerebral infarction and investigate its mechanism. METHODS: Sixty rats were randomly divided into a sham operation group, an acupuncture group and a non-acupuncture group, and each group was randomly divided into a 1-day subgroup, a 7-day subgroup and a 14-day subgroup. Cerebral infarction model was induced by the thread embolism method. The rats in the acupuncture group were treated by electroacupuncture at "Zusanli" (ST 36) and "Neiguan" (PC 6) for 20 minutes, once each day, while the rats in the sham operation group and the non-acupuncture group were just bound and fixed at the same time without acupuncture treatment. Neurological defects were assessed by Neurological Severity Score (NSS) and the changes of the expression of growth associated protein 43 (GAP-43) in peripheral nerve around cerebral infarction area were detected by immunohistochemistry technique. RESULTS: The expression of the positive cells of GAP-43 around cerebral infarction area showed no significant distinction among the three groups at 1st day (P > 0.05), while the GAP-43 expression level of around cerebral infarction area in the acupuncture group (IOD:8. 990 1 +/- 0.098 7, 5.816 1 +/- 0.204 6) were significant higher than those in the sham operation group (IOD: 1.300 2 +/- 0.093 3, 1.362 6 +/- 0.216 6) and in the non-acupuncture group (IOD: 2.753 4 +/- 0.0875, 1.616 5 +/- 0.186 8) at 7th day and 14th day, respectively (all P < 0.01). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) and "Neiguan" (PC 6) can improve the neural function and promote its remodeling in rats with cerebral infarction and the relevant mechanisms may be involved in enhancement of GAP-43 expressions around ischemic region.