An impaired ability to regulate microglia activation by fractalkine (CX3CL1) leads to microglia chronic sub-activation. How this condition affects outcome after acute brain injury is still debated, with studies showing contrasting results depending on the timing and the brain pathology. Here, we investigated the early and delayed consequences of fractalkine receptor (CX3CR1) deletion on neurological outcome and on the phenotypical features of the myeloid cells present in the lesions of mice with traumatic brain injury (TBI). Wild type (WT) and CX3CR1 -/-C57Bl/6 mice were subjected to sham or controlled cortical impact brain injury. Outcome was assessed at 4 days and 5 weeks after TBI by neuroscore, neuronal count, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Compared with WT mice, CX3CR1 -/-TBI mice showed a significant reduction of sensorimotor deficits and lower cellular damage in the injured cortex 4 days post-TBI. Conversely, at 5 weeks, they showed a worsening of sensorimotor deficits and pericontusional cell death. Microglia (M) and macrophage (l) activation and polarization were assessed by quantitative immunohistochemistry for CD11b, CD68, Ym1, and inducible nitric oxide synthase (iNOS)-markers of M/l activation, phagocytosis, M2, and M1 phenotypes, respectively. Morphological analysis revealed a decreased area and perimeter of CD11b + cells in CX3CR1 -/-mice at 4 days post-TBI, whereas, at 5 weeks, both parameters were significantly higher, compared with WT mice. At 4 days, CX3CR1 -/-mice showed significantly decreased CD68 and iNOS immunoreactivity, while at 5 weeks post-injury, they showed a selective increase of iNOS. Gene expression on CD11b + sorted cells revealed an increase of interleukin 10 and insulin-like growth factor 1 (IGF1) at 1 day and a decrease of IGF1 4 days and 5 weeks post-TBI in CX3CR1 -/-, compared with WT mice. These data show an early protection followed by a chronic exacerbation of TBI outcome in the absence of CX3CR1. Thus, longitudinal effects of myeloid cell manipulation at different stages of pathology should be investigated to understand how and when their modulation may offer therapeutic chances.

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The signaling pathway of chronic morphine treatment to prevent neuronal damage following transient cerebral ischemia is not clear. In this study, we examined the role of mammalian target of rapamycin (mTOR) to identify the neuroprotective effects of chronic morphine preconditioning on the hippocampus following ischemia-reperfusion (I/R) injury. Morphine was administered for 5 days, twice a day, before inducing I/R injury. The possible role of mTOR was evaluated by the injection of rapamycin (5 mg/kg body weight, by intraperitoneal injection) before I/R was induced. The passive avoidance test was used to evaluate memory performance. Neuronal density and apoptosis were measured in the CA1 region, 72 h after I/R injury. The expressions of mTOR and phosphorylated mTOR (p-mTOR), as well as superoxide dismutase (SOD) activity were determined 24 h after I/R injury. Chronic morphine treatment attenuated apoptosis and neuronal loss in the hippocampus after I/R injury, which led to improvement in memory (P < 0.05 vs. untreated I/R) and increase in the expression of p-mTOR (P < 0.05 vs. untreated I/R) and SOD activity (P < 0.05 vs. untreated I/R) in the hippocampus. Pretreatment with rapamycin abolished all the above-mentioned protective effects. These results describe novel findings whereby chronic morphine preconditioning in hippocampal CA1 neurons is mediated by the mTOR pathway, and through increased phosphorylation of mTOR can alleviate oxidative stress and apoptosis, and eventually protect the hippocampus from I/R injury.

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Introduction: The autologous pericardium, treated or fresh, is used in reconstructive cardiovascular surgery. We aimed to describe the features of fresh pericardium utilized in right ventricular outflow tract (RVOT) reconstruction, years after the initial surgery. Methods: This cross-sectional study was performed on 72 patients (65.3% male, mean age =18.68 ± 9.63 y) with a history of RVOT reconstruction with the fresh autologous pericardium who underwent reoperation. During the surgery, a 1 × 1 cm sample was cut from the previous pericardial patch, and hematoxylin and eosin (H & E), Masson’s trichrome, and immunohistochemistry (IHC) staining was conducted. All the stained slides were evaluated,and the descriptive results were explained. Results: The mean follow-up duration was 13.48 ± 7.38 years. In preoperative evaluations,53 (73.6%) patients exhibited no RVOT dilatation, 17 (23.6%) showed mild RVOT dilatation,and 2 (2.8%) had RVOT aneurysms. The H & E staining revealed no calcification in 80.55%(58/72), mild calcification in 9.72% (7/72), and moderate calcification in 9.72% (7/72) of the total samples. None of the specimens demonstrated a marked calcification. All the samples were positive for CD31, CD34, smooth muscle alpha-actin, and von Willebrand factor in IHC. In Masson’s trichrome staining, on average, 64.74% (±18.61) of the tissue sections contained collagen fibers. Conclusion: The fresh autologous pericardium, utilized for RVOT reconstruction, showed viability, growth potential, positivity for endothelial cell markers, vascular differentiation,insignificant calcification, and no stenosis at long-term follow-up. We would, therefore, suggest it as a suitable choice for such reconstructive operations. Moreover, its usage during total correction of tetralogy of Fallot could be safe, feasible, and durable.