minocycline and Hematoma

The complement cascade is activated and may play an important pathophysiologic role in brain injury after experimental intracerebral hemorrhage (ICH). However, the exact mechanism of specific complement components has not been well studied. This study determined the role of complement C1q/C3-CR3 signaling in brain injury after ICH in mice. The effect of minocycline on C1q/C3-CR3 signaling-induced brain damage was also examined.. There were three parts to the study. First, the natural time course of C1q and CR3 expression was determined within 7 days after ICH. Second, mice had an ICH with CR3 agonists, LA-1 or vehicle. Behavioral score, neuronal cell death, hematoma volume, and oxidative stress response were assessed at 7 days after ICH. Third, the effect of minocycline on C1q/C3-CR3 signaling and brain damage was examined.. There were increased numbers of C1q-positive and CR3-positive cells after ICH. Almost all perihematomal C1q-positive and CR3-positive cells were microglia/macrophages. CR3 agonist LA-1 aggravated neurological dysfunction, neuronal cell death, and oxidative stress response on day 7 after ICH, as well as enhancing the expression of the CD163/HO-1 pathway and accelerating hematoma resolution. Minocycline treatment exerted neuroprotective effects on brain injury following ICH, partly due to the inhibition of C1q/C3-CR3 signaling, and that could be reversed by LA-1.. The complement C1q/C3-CR3 signaling is upregulated after ICH. The activation of C1q/C3-CR3 signaling by LA-1 aggravates brain injury following ICH. The neuroprotection of minocycline, at least partly, is involved with the repression of the C1q/C3-CR3 signaling pathway.

Topics: Animals; Brain Injuries; Cerebral Hemorrhage; Complement C1q; Hematoma; Mice; Minocycline; Neuroprotective Agents; Signal Transduction

The role of surgery for most patients with spontaneous intracerebral haemorrhage (ICH) remains controversial due to the continuous occurrence of postoperative iron overload induced by low clot clearance rate. In this study, human hair keratose hydrogel (KG) loading with minocycline hydrochloride (MH) were prepared to reduce iron overload for the improvement of the postoperative functional recovery after ICH aspiration surgery. Hemoglobin-induced iron accumulation in rat primary neuronal culture was delayed by the adsorptive capacity of blank KG, while MH-loaded KG displayed a stronger and more thorough cytoprotective effect than blank KG due to the combined effect of absorptive action to iron and sustained release of the iron chelator. Moreover, high iron-chelating efficiency in the hematoma region supplied by MH-loaded KG significantly reduced dose strength of iron chelator. In situ injection of KG with different MH loadings (2, 20, and 200μg) into the hematoma region after aspiration surgery showed a stronger effect on the reduction of ICH-induced iron accumulation, edema, and neurological deficits in rats compared to the postoperative intraperitoneal administration of MH (approximately 15mg). These results suggested that the in situ KG not only could effectively reduce the ICH postoperative iron overload and improve the postoperative functional recovery via the iron adsorption and sustained release of MH, but also has great potential to reduce the systemic adverse effects by decreasing the dose strength of iron chelator.

Topics: Animals; Cerebral Hemorrhage; Chelating Agents; Delayed-Action Preparations; Disease Models, Animal; Female; Hematoma; Hemoglobins; Humans; Hydrogels; Iron; Iron Overload; Keratosis; Male; Minocycline; Neurons; Postoperative Hemorrhage; Pregnancy; Rats; Rats, Sprague-Dawley

This study sought to determine whether the nonabsorbable TYRX Antibacterial Envelope (TYRX) reduces major cardiovascular implantable electronic device (CIED) infections 12 months after implant.. TYRX is a monofilament polypropylene mesh impregnated with minocycline and rifampin specifically designed to hold a CIED in place and elute antimicrobials over time. There are limited data on its ability to reduce CIED infections.. We prospectively enrolled patients who underwent generator replacement with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT), treated with TYRX. The primary endpoints were major CIED infection and CIED mechanical complications. Given the differences in infection rates among ICD and CRT patients, 3 different control populations were used: a published benchmark rate for ICD patients, and both site-matched and comorbidity-matched controls groups for CRT patients.. Overall, a major CIED infection occurred in 5 of 1,129 patients treated with TYRX (0.4%; 95% confidence interval: 0.0% to 0.9%), significantly lower than the 12-month benchmark rate of 2.2% (p = 0.0023). Among the TYRX-treated CRT cohort, the major CIED infection rate was 0.7% compared with an infection rate of 1.0% and 1.3% (p = 0.38 and p = 0.02) in site-matched and comorbidity-matched control groups, respectively. Among the ICD group, the 12-month infection rate was 0.2% compared with the published benchmark of 2.2% (p = 0.0052). The most common CIED mechanical complication in study patients was pocket hematoma, which occurred in 18 of the 1,129 patients (1.6%; 95% confidence interval: 0.8 to 2.5), which is comparable with a published rate of 1.6%.. Use of TYRX was associated with a lower major CIED infection rate. (TYRX™ Envelope for Prevention of Infection Following Replacement With a CRT or ICD; [Centurion]; NCT01043861/NCT01043705).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cardiac Resynchronization Therapy; Defibrillators, Implantable; Delayed-Action Preparations; Female; Follow-Up Studies; Hematoma; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Prosthesis-Related Infections; Reoperation; Rifampin; Risk Factors; Surgical Mesh