Immunity and stroke, the hurdles of stroke research translation

Immunomodulatory therapies after stroke have the potential to provide clinical benefit to a subset of patients, but risk subverting the protective, healing aspects of the innate immune response. Neutrophils clear necrotic cerebral tissue and are important in immunomodulation, but can also contribute to tissue injury. Human trials for immunomodulatory stroke treatments in the sub-acute time frame have attempted to prevent peripheral neutrophil infiltration, but none have been successful and one trial demonstrated harm. These unselected trials had broad inclusion criteria and appear to not have had a specific treatment target. Unfortunately, due to the heterogeneous nature of brain ischemia in humans resulting in variation in clinical severity, the negative effect of thrombolytic drugs on the blood-brain barrier, and the heterogeneity of immune response, it may only be a subset of stroke patients who can realistically benefit from immunomodulation therapies. Translational research strategies require both an understanding of lab practices which create highly controlled environments in contrast to clinical practice where the diagnosis of stroke does not require the identification of a vessel occlusion. These differences between lab and clinical practices can be resolved through the integration of appropriate patient selection criteria and use of advanced imaging and ridged patient selection practices in clinical trials which will be an important part to the success of any future trials of translational research such as immunomodulation.