Abstract 2156: Minocycline-induced Attenuation Of Iron Overload And Brain Injury Following Experimental Intracerebral Hemorrhage

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Fan Zhao ◽  
Ya Hua ◽  
Richard F Keep ◽  
Guohua Xi
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Iron Overload ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Neuronal Death ◽  
Total Iron ◽  
Brain Barrier ◽  
Brain Iron ◽  
Blood Brain

Background and Purpose: 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. Methods: This study was divided into three parts. (1) Male Sprague-Dawley 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. Rats were euthanized 1, 3 and 7 days later for serum iron, brain iron, and brain iron handling protein measurements. (3) Rats had a 50µl intracaudate injection of either saline, FeCl2, FeCl2+minocycline or FeCl2+macrophage/microglia inhibitory factor and were euthanized at one day later for measurements of brain edema, blood-brain barrier disruption and neuronal death. Results: After ICH, serum total iron and brain non-heme iron increased and these changes were reduced by minocycline treatment (e.g. serum total iron at day 3: 158±36 vs. 245±22 µg/dL in the vehicle-treated group, p<0.01). 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 co-injection with minocycline (p<0.05). Conclusions: 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 ICH patients because both iron accumulation and microglia activation contribute to brain damage following ICH.

scholarly journals Minocycline-Induced Attenuation of Iron Overload and Brain Injury After Experimental Intracerebral Hemorrhage

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3587-3593 ◽  
Author(s):  
Fan Zhao ◽  
Ya Hua ◽  
Yangdong He ◽  
Richard F. Keep ◽  
Guohua Xi
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Iron Overload ◽  
Brain Edema ◽  
Neuronal Death ◽  
Iron Chelator ◽  
Total Iron ◽  
Brain Iron

Background and Purpose— 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. Methods— 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. Results— 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. Conclusions— 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.

The effects of lornoxicam on brain edema and blood brain barrier following diffuse traumatic brain injury in rats

2013 ◽  
Vol 19 (4) ◽  
pp. 294-298 ◽  
Author(s):  
Ismet Topcu ◽  
Gul Gumuser ◽  
Eda Bayram ◽  
Feray Aras ◽  
Ismail Cetin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals GOLGA2/GM130 is a novel target of neuroprotection therapy in intracerebral hemorrhage

2021 ◽  
Author(s):  
shu wen deng ◽  
Qing Hu ◽  
Qiang He ◽  
Xi qian Chen ◽  
Qiang Lei ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Water Content ◽  
Autophagy Flux ◽  
Blood Brain ◽  
Brain Water

Abstract Background Impairment of the blood-brain barrier after intracerebral hemorrhage (ICH) can lead to secondary brain injury and aggravate neurological deficits. Owing in part to our lack of understanding of the mechanism of ICH injury to the blood-brain barrier, there are currently no effective methods to prevent or treat it. Here, we explored the effects of Golgi apparatus protein GM130 overexpression or silencing on the blood-brain barrier and neurological function after ICH, to better understand the mechanism involved and facilitate the development of new therapeutic methods. Results Levels of the tight junction-associated proteins ZO-1 and occludin decreased, while those of LC3-II, a marker for autophagosomes, increased in hemin-treated Bend.3 cells (p < 0.05). The levels of ZO-1 and occludin increased, while those of LC3-II decreased with GM130 overexpression (p < 0.05). ZO-1 and occludin expression decreased and LC3-II increased after siGM130 transfection, mimicking the effect of hemin (p < 0.05). Tight junctions were disconnected after hemin or siGM130 treatment and repaired with GM130 overexpression. siGM130 transfection in Bend.3 cells increased autophagy flux, whereas GM130 overexpression downregulated autophagy flux. Similar results were verified in an in vivo ICH model. Perihematomal ZO-1 and occludin expression increased, while LC3-II expression decreased in ICH rats (p < 0.05). ZO-1 and occluding expression further decreased and LC3-II expression increased in siGM130-treated ICH rats (p < 0.05), whereas a reverse effect was observed in AAV-GM130-treated ICH rats (p < 0.05). Perihematomal Evans blue and brain water content were much higher in siGM130-treated ICH rats than in the control ICH rats. AAV-GM130-treated ICH rats showed a lower perihematomal Evans blue and brain water content than the control ICH rats. Conclusions GM130 overexpression can protect the integrity of the blood-brain barrier from brain injury, inhibit excessive autophagy flux in an ICH in vivo model, and further improve the neurobehavioral prognosis. GM130 overexpression may mediate tight junction protein repair by directly reducing autophagy flux in an ICH in vitro model. GM130 may be a therapeutic target for acute brain injury after ICH.

Neuroprotective effects of citicoline on brain edema and blood—brain barrier breakdown after traumatic brain injury

2000 ◽  
Vol 92 (3) ◽  
pp. 448-452 ◽  
Author(s):  
Mustafa K. Başkaya ◽  
Aclan Doğan ◽  
A. Muralikrishna Rao ◽  
Robert J. Dempsey
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blue Dye ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Blood Brain ◽  
Fine Print

Object. Cytidine 5′-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI.Methods. After anesthesia had been induced in Sprague—Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet—dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight–10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5′-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/kg of CDPC significantly decreased brain edema and BBB breakdown.Conclusions. This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.

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