minocycline and Iron-Overload

Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2

Topics: Aging; Animals; Brain; Brain Injuries; Cerebral Hemorrhage; Female; Iron Overload; Minocycline; Neuroprotective Agents; Rats; Rats, Inbred F344

Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined.. Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points.. ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits (. Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats.

Topics: Animals; Anti-Bacterial Agents; Blotting, Western; Brain; Cell Death; Cerebral Hemorrhage; Disease Models, Animal; Dopamine and cAMP-Regulated Phosphoprotein 32; Ferritins; Heme Oxygenase (Decyclizing); Immunohistochemistry; Iron Overload; Magnetic Resonance Imaging; Male; Minocycline; Neurons; Rats; Rats, Inbred F344

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

Germinal matrix hemorrhage (GMH) is the most important adverse neurologic event during the newborn period. Evidence has shown that neonates with GMH and hydrocephalus have more severe damage compared to those with GMH alone. Our preliminary study demonstrated the role of iron in hydrocephalus and brain damage in adult rats following intraventricular hemorrhage. Therefore, the aim of the current study was to investigate iron accumulation and iron-handling proteins in a rat model of GMH and whether minocycline reduces iron overload after GMH and iron-induced brain injury in vivo. This study was divided into two parts. In the first part, rats received either a needle insertion or an intracerebral injection of 0.3 U of clostridial collagenase VII-S. Brain iron and brain iron handling proteins (heme oxygenase-1 and ferritin) were measured. In the second part, rats with a GMH were treated with minocycline or vehicle. Brain edema, brain cell death, hydrocephalus, iron-handling proteins and long-term motor function were examined. The result showed iron accumulation and upregulation of iron-handling proteins after GMH. Minocycline treatment significantly reduced GMH-induced brain edema, hydrocephalus and brain damage. Minocycline also suppressed upregulation of ferritin after GMH. In conclusion, the current study found that iron plays a role in brain injury following GMH and that minocycline reduces iron overload after GMH and iron-induced brain injury.

Topics: Animals; Blotting, Western; Brain Edema; Cerebral Hemorrhage; Disease Models, Animal; Immunohistochemistry; In Situ Nick-End Labeling; Iron Overload; Minocycline; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo.. This study was divided into 4 parts: (1) rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination; (2) rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured; (3) rats had an intracaudate injection of saline, iron, iron+minocycline, or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements; and (4) rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement.. After ICH, serum total iron and brain nonheme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage, and brain cell death, all of which were significantly reduced by coinjection with minocycline.. The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for patients with ICH because both iron accumulation and microglia activation contribute to brain damage after ICH.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Injuries; Cell Count; Cell Death; Cerebral Hemorrhage; Iron; Iron Overload; Male; Microglia; Minocycline; Neurons; Rats; Rats, Sprague-Dawley