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As the population is aging all over the world, the economic burden of ischemic brain injuries is constantly increasing. Human brain ischemia is one of the leading causes of premature death, significant morbidity and physical and mental disabilities, resulting in a lower quality of life and unusually high costs of health and social care. One of the most difficult problems associated with the pathology of the brain after ischemia is progressive dementia observed in people who survived the stroke. More recently, brain ischemia has been shown to elicit Alzheimer's disease neuropathologic change, possibly facilitating the development of dementia due to the amyloidogenic processing of Alzheimer's disease-related amyloid protein precursor into amyloid. The main purpose of this review is to present the development of Alzheimer's disease neuropathologic change in the brain after human and experimental ischemia, with a particular emphasis on proteins and genes involved in the amyloidogenic processing of the amyloid protein precursor to amyloid.

In elderly population, Alzheimer's disease is a common neurodegenerative disorder and accounts for about 70% of all cases of dementia. The neurodegenerative processes of this disease start presumably 20 years ahead of the clinical beginning of the disorder. The postmortem histopathological examination, brains from Alzheimer's disease patients with characteristic features like amyloid plaques and neurofibrillary tangles, neuronal and synaptic disintegration confirm the final diagnosis of Alzheimer's disease. Senile plaques are composed of -amyloid peptide, deriving from the amyloid protein precursor, which is present not only in the brain tissue, but also in other non-neuronal tissues. Some investigations reported that platelets possess amyloid protein precursor and all the enzymatic activities required for the metabolism of this protein throughout the same pathways present in the brain. Thus, platelets may be a good peripheral blood cell-based biomarker to study the onset of Alzheimer's disease. Another line of research indicated molecular and cellular aberrations in blood lymphocytes and erythrocytes from Alzheimer's disease patients and emphasizes the systemic nature of the disease. In this review, we will summarize the recent knowledge on the involvement and/or response of platelets, lymphocytes and red blood cells in the circulation during Alzheimer's disease development. The facts will be reviewed with the special possibility for applying the above blood cells as Alzheimer's disease preclinical and antemortem blood cell-based biomarkers.

Cardiac arrest, usually occurring in the aged population, is the most important cause of high morbidity and death in developed countries. Commonly, attention, depression, cognitive impairment, spatial memory, short- and long-term memory, executive functions, decreased quality of life and social participation are disturbed following circulation arrest. Deficits in cognitive function, similar to prodromal Alzheimer's disease dementia, following cardiac arrest remain an area of concern. Recent research has focused on the post-resuscitation period to identify mechanisms of long-term brain damage and cognitive impairment. As more patients survive longer periods after cardiac arrest, attention is focused on interventions that may enhance cognitive and psychosocial perceptions. Here, we review the new data influencing the cognitive and functional outcome in the post-resuscitation period. .

Transient cardiac arrest due to cardiac vessel bundle occlusion was used to produce a rat model of spontaneous and audiogenic seizures. Among the rats, spontaneous seizures were present in 64%, and audiogenic seizures could be evoked in 86%, during two weeks of survival after cardiac arrest, by exposure to a loud sound produced by rattling keys, beginning one day after the post-ischaemic injury. Data from literature suggested a key role for GABA-ergic system widespread dysfunction especially in the hippocampus in post-cardiac arrest onset of audiogenic seizures. Reduced GABA inhibition in the hippocampus seems responsible for audiogenic seizures following cardiac arrest. In summary it may be considered that the occurrence of audiogenic seizures following cardiac arrest is determined not only by a neuronal loss, especially in the hippocampus, but also by a condition of synapse modification by a regenerative phenomenon. Data from our study clearly indicate that global brain ischaemia due to cardiac arrest may induce the susceptibility to spontaneous and audiogenic seizures, but this effect is transient.

For thousands of years, humankind has used plants for therapeutics. Nowadays, there is a renewed public interest in naturally occurring treatments with minimal toxicity and diets related to health. Alterations in hippocampal neurogenesis have been recognized as an integral part of brain ischemia. Neuronal stem/progenitor cells in the hippocampus are positively and negatively regulated by intrinsic and extrinsic agents. One positive regulator of neurogenesis in the hippocampus is curcumin in the diet. This review provides an assessment of the current state of the field in hippocampal neurogenesis and neuroprotection studies in brain ischemia and focuses on the role of curcumin in the diet. Data suggest that dietary intake of curcumin enhances neurogenesis. Recent studies performed in ischemic models have suggested that curcumin also has neuroprotective features. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent ageing-associated changes in cellular proteins that lead to protein insolubility and aggregation after ischemia such as β-amyloid peptide and tau protein. Here, we also review the evidence from ischemic models that curcumin improves cognition and health span by overexpression of life supporting genes and preventing or delaying the onset of neurodegenerative changes. Available data provide evidence that curcumin induces neurogenesis and neuroprotection and may provide a novel therapeutic agent for both regenerative medicine and for the treatment of neurodegenerative diseases such as postischemic brain neurodegeneration with Alzheimer phenotype.

In this paper we review the hard-earned data, which present ischemic induction of amyloid precursor protein, presenilins, apolipoproteins and secretases genes, playing key roles in β-amyloid peptide generation. Presented data are strongly supporting a hypothesis that brain ischemia may be involved in the aetiology of sporadic Alzheimer's disease. Potential contribution and impact of ischemically activated genes on the development of sporadic Alzheimer's disease remain to be established at both genetic and functional levels. The identification of the genes involved in sporadic Alzheimer's disease induced by ischemia will enable to further define the events leading to Alzheimer's disease-related abnormalities. Additionally, knowledge gained from the reviewed studies should facilitate the elaboration of effective treatment and/or prevention of sporadic Alzheimer's disease.