Clinico-pathological correlations in fatal ischemic stroke. An immunohistochemical study of human brain penumbra

Ischemic stroke is one of the most frequent pathologies with high invalidating potential and a leading cause of death. The brain tissue adjacent to the central necrotic core, defined as penumbra, was extensively characterized mostly by imaging techniques and in animal models. Our goal was to identify a large panel of molecules in this particular area on human brains harvested at autopsy. Twenty-one patients with ischemic stroke and seven control cases were taken into study. We used immunohistochemistry to characterize necrotic lesions. Metalloproteinases, mostly MMP-9, seem to be involved in brain ischemia, but as a protective and not as a deleterious factor. Apoptotic molecules are not increasingly expressed in stroke compared to control cases. Mast cell enzymes chymase and tryptase are described for the first time in neurons and glia, even with unclear significance. Microglia appears active in stroke and stimulating methods directed to it could be useful. Nitric oxide synthases and cyclooxygenase-2 were also involved in stroke cases but not in control ones. Other factors as VEGF and its receptors, PDGF, b-FGF or TNF-alpha showed no significant expression related to ischemic brain injury. Animal study of penumbra and human tissue findings are distinct and research should be focused on the latter approach in order to find valuable and safe therapeutic methods.