The combination of deferoxamine and minocycline strengthens neuroprotective effect on acute intracerebral hemorrhage in rats

ABSTRACT

Objectives: Intracerebral hemorrhage (ICH) is a devastating type of strokes that carries high mortality rates, but effective therapeutic options are still lacking. Here, the adult rat model of ICH was used to investigate the efficacy of a combinational therapy of deferoxamine (DFX) and minocycline.

Methods: The ICH was induced by stereotaxic infusion of collagenase into striatum of adult rats. After the induction of ICH, rats were treated with intraperitoneal injection of deferoxamine (50 mg/kg), minocycline (45 mg/kg), or both agents, at 2 hours after ICH and then every 12 hours for up to 3 days. The vehicle group were treated with phosphate-buffered saline (PBS) only. Rats were killed at 1, 2, and 3 day(s) for examination of iron deposition, neuronal death, neurological deficits, the area of brain damage, activation of microglia/macrophages.

Results: Our data revealed that the systemic administration of DFX and/or minocycline decreased iron accumulation. And immunofluorescence staining results indicated that drug-treated group significantly decreased the neuronal degeneration, the number of activated microglia/macrophages and the amount of cell death after ICH. In addition, neurological deficits caused by ICH were improved in the presence of DFX and/or minocycline compare with vehicle group. Furthermore, the combination treatment showed better effects in neuroprotection and anti-inflammation when compared to the monotherapy groups.

Conclusions: The combination therapy significantly reduces the number of neuronal deaths, suppresses of the activation of microglia/macrophages, decreases iron accumulation in the area around the hematoma, lessening the brain damage area, and improving neurological deficits in ICH.

KEYWORDS:

• Intracerebral hemorrhage
• inflammation
• iron
• neuroprotection
• deferoxamine
• minocycline

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the author(s).

Statement of authorship

ZL wrote the first manuscript and drew the images; YL, RW, and SK searched and organized the papers; VWY edited the manuscript; MX supervised the project.

Data sharing statement

No additional data are available.

Additional information

Funding

The authors acknowledge operating grant support from the National Natural Science Foundation of China [82071331, 81870942, and 81520108011], National Key Research and Development Program of China [2018YFC1312200], and Innovation Scientists and Technicians Troop Constructions Projects of Henan Province of China (for MX); Research grant from China Postdoctoral Science Foundation [2020TQ0289 for RW, 2020M672291for SK]; and from the Canadian Institutes of Health Sciences (VWY).