There is increasing evidence for influence of Alzheimer's proteins and neuropathology on ischemic brain injury. This review investigates the relationships between b-amyloid peptide, apolipoproteins, presenilins, tau protein, a-synuclein, inflammation factors, and neuronal survival/ death decisions in brain following ischemic episode. The interactions of these molecules and influence on b-amyloid peptide synthesis and contribution to ischemic brain degeneration and finally to dementia are reviewed. Generation and deposition of b-amyloid peptide and tau protein pathology are important key players involved in mechanisms in ischemic neurodegeneration as well as in Alzheimer's disease. Current evidence suggests that inflammatory process represents next component, which significantly contribute to degeneration progression. Although inflammation was initially thought to arise secondary to ischemic neurodegeneration, recent studies present that inflammatory mediators may stimulate amyloid precursor protein metabolism by upregulation of b-secretase and therefore are able to establish a vicious cycle. Functional brain recovery after ischemic lesion was delayed and incomplete by an injuryrelated increase in the amount of the neurotoxic C-terminal of amyloid precursor protein and b-amyloid peptide. Moreover, ischemic neurodegeneration is strongly accelerated with aging, too. New therapeutic alternatives targeting these proteins and repairing related neuronal changes are under development for the treatment of ischemic brain consequences including memory loss prevention.

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MRI was employed to follow the neurodegenerative foci and the localization of inflammatory cells by magnetically labeled CD4+ or CD8+ lymphocytes in the ischemia/reperfusion long-lived rats (9 and 13 months after 10 min of cardiac arrest). MRI of ischemic rats showed: (1) blood-brain barrier (BBB) leakage in the area of the dorsal hippocampus and brainstem-hindbrain level in basal cerebellum, (2) unlike anti-CD8 magnetic antibodies anti-CD4 ultra small paramagnetic iron oxide particles (USPIO) antibodies revealed hypointense areas in the brainstem-interbrain region and caudoputamen not found in animals that were not injected with USPIO antibodies, and (3) dilation in the retrosplenial area. Immunocytochemistry revealed microglial activation in the hippocampus and striatum, with indications of activation in thalamic lateral dorsal nuclei and the subventricular zone. In the CA1 and CA3 regions, it was noted that OX42- and ED1-positive granules appear in neuronal somata. Immunostaining of lymphocytes with TCR confirmed the T-cell presence in ischemic brain parenchyma of the hippocampus and striatum. The above observations thus point to a persistent dysfunction of BBB that in long-term may still lead to infiltration of T cells that are predominantly of helper (CD4+) type. Such inflammatory processes are backed by microglial activity even up to 1 year after ischemia/reperfusion. Moreover, in these animals an augmented expression of neurogenesis markers and neuroblast migration was also revealed in the subventricular zone. Thus, a balance of degenerative processes and inflammatory surveillance with neurogenesis could determine the long-term outcome of global ischemia survival or the previously proposed formation of amyloid plaques and Alzheimer's-type dementia.