The "inflammatory penumbra" in ischemic stroke: From clinical data to experimental evidence

The objective of the present review is to provide an overview of the available clinical and preclinical data supporting the existence of an "inflammatory penumbra" in ischemic stroke.

Recent data from clinical trials suggest the existence of an inflammatory area at risk, surrounding the initial ischemic lesion and secondarily infiltrated by lymphocytes, that is ultimately recruited by the ischemic core: called the "inflammatory penumbra." Experimental results support this concept. Lymphocytes, especially T-cells, enter the brain in the perilesional area in a vascular-cell adhesion molecule-1 dependent manner and participate in delayed neuronal cell death.

For writing this review, we used the more recent publications in the field, including the preclinical and clinical studies. We have also used our own experise in the field of in vivo imaging of inflammatory processes.

Consequently, the intensity of the inflammatory reaction and the size of the inflammatory penumbra may vary considerably in patients, as it is the case in experimental stroke models in mice. By analogy with the ischemic penumbra of the acute phase of stroke, this secondary inflammatory penumbra represents a therapeutic opportunity during the subacute phase of stroke. Large clinical trials that target lymphocyte trafficking are currently taking place. However, to improve the benefit of such therapeutic strategies, adequate patient selection may be mandatory.

In this context, innovative imaging methods including magnetic resonance imaging of adhesion molecules may contribute to noninvasively detect this inflammatory penumbra and thus to select patients eligible for such therapy.