Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage

Journal of Neuroinflammation

Michael L James³  Daniel T Laskowitz²  Haichen Wang³  Briana Roulhac-Wilson⁴  Hana N Dawson³  Beilei Lei¹ 

[1] Department of Anesthesiology, DUMC - 3094, Durham, NC 27710, USA;Department of Neurobiology, DUMC - 3209, Durham, NC 27710, USA;Department of Neurology, DUMC - 2900, Durham, NC 27710, USA;Multidisciplinary Neuroprotection Laboratories, 132 Sands Bldg, Durham, NC 27710, USA

关键词: Remicade;    Cytokine;    Murine model;    Tumor necrosis factor alpha antagonism;    Microglia;    Intracerebral hemorrhage;   

Others  :  1152304
DOI  :  10.1186/1742-2094-10-103

 received in 2013-03-27, accepted in 2013-08-02,  发布年份 2013

【 摘 要 】

Background

Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by a prominent neuroinflammatory response. Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH. To test this hypothesis, the tumor necrosis factor alpha (TNF-α) antibody CNTO5048 was administered to mice after ICH induction, and histological and functional endpoints were assessed.

Methods

Using 10 to 12-week-old C57BL/6J male mice, ICH was induced by collagenase injection into the left basal ganglia. Brain TNF-α concentration, microglia activation/macrophage recruitment, hematoma volume, cerebral edema, and rotorod latency were assessed in mice treated with the TNF-α antibody, CNTO5048, or vehicle.

Results

After ICH induction, mice treated with CNTO5048 demonstrated reduction in microglial activation/macrophage recruitment compared to vehicle-treated animals, as assessed by unbiased stereology (P = 0.049). This reduction in F4/80-positive cells was associated with a reduction in cleaved caspase-3 (P = 0.046) and cerebral edema (P = 0.026) despite similar hematoma volumes, when compared to mice treated with vehicle control. Treatment with CNTO5048 after ICH induction was associated with a reduction in functional deficit when compared to mice treated with vehicle control, as assessed by rotorod latencies (P = 0.024).

Conclusions

Post-injury treatment with the TNF-α antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH.

【 授权许可】

   
2013 Lei et al.; licensee BioMed Central Ltd.

【 图 表 】

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