Neuroscience
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Transient global ischemia selectively damages neurons in specific brain areas. A reproducible pattern of selective vulnerability is observed in the dorsal hippocampus of rodents where ischemic damage typically affects neurons in the CA1 area while sparing neurons in CA3 and granule cells. The "neuronal factors" underlying the differential vulnerability of CA1 versus CA3 have been of great interest. ⋯ A survey of selective vulnerability in the human hippocampus in relation to genomic studies in ischemia-hypoxia is presented, and neurodegeneration genes with high expression in CA1 are highlighted (e.g. WFS1). It is concluded that neuronal factors dominate the selective vulnerability of CA1 but that vascular factors also deserve more systematic studies.
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A consequence of normal aging is a greater susceptibility to memory impairments following an immune challenge such as infection, surgery, or traumatic brain injury. The neuroinflammatory response, produced by these challenges results in increased and prolonged production of pro-inflammatory cytokines in the otherwise healthy aged brain. ⋯ We review the current understanding of the causes and effects of normal aging-induced microglial sensitization, including dysregulations of the neuroendocrine system, potentiation of neuroinflammatory responses following an immune challenge, and the impairment of memories. We end with a discussion of therapeutic approaches to prevent these deleterious effects.
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Clinical studies suggest that obesity and Type 2 (insulin-resistant) diabetes impair the structural integrity of medial temporal lobe regions involved in memory and confer greater vulnerability to neurological insults. While eliminating obesity and its endocrine comorbidities would be the most straightforward way to minimize cognitive risk, structural barriers to physical activity and the widespread availability of calorically dense, highly palatable foods will likely necessitate additional strategies to maintain brain health over the lifespan. Research in rodents has identified numerous correlates of hippocampal functional impairment in obesity and diabetes, with several studies demonstrating causality in subsequent mechanistic studies. ⋯ This review discusses these findings with reference to the benefits of incorporating existing models from the fields of obesity and metabolic disease. Many transgenic lines with basal metabolic alterations or differential susceptibility to diet-induced obesity have yet to be characterized with respect to their cognitive and synaptic phenotype. Adopting these models, and building on the extensive knowledge base used to generate them, is a promising avenue for understanding interactions between peripheral disease states and neurodegenerative disorders.
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Epileptogenesis refers to the development and extension of tissue capable of generating spontaneous seizures, resulting in the development of an epileptic condition and/or progression of epilepsy after the condition is established. The hippocampus is the seizure-initiating zone in many epilepsy patients as well as in animal models of epilepsy. During epileptogenesis, the hippocampus undergoes structural changes, including mossy fiber sprouting; alterations in dendritic branching, spine density, and shape; and neurogenesis. ⋯ Here we review conventional and more advanced MRI methods for detecting hippocampal tissue changes related to epileptogenesis. In addition, we summarize how diffusion tensor imaging can reveal cellular damage and plasticity, even at the level of hippocampal subfields. Finally, we discuss challenges and future directions for using novel MRI techniques in the search of biomarkers associated with epileptogenesis after brain injury.
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For over two decades it has been increasingly appreciated that synaptic plasticity mechanisms are subject to activity-dependent metaplastic regulation. In recent years it has also become apparent that astrocytes are active partners with neurons at synapses, and have the capability to powerfully regulate synaptic plasticity. However, the field of astrocyte-mediated metaplasticity is still very much in its infancy. ⋯ This contribution may be particularly important given that altered plasticity in the hippocampus is a hallmark of several disease states. The known ways by which astrocytes exert metaplasticity are reviewed here, and hypothetical mechanisms of astrocyte-mediated metaplasticity are considered for the benefit of future investigation. The latter half of this review focuses on what part these mechanisms, and others, may play in the diseased or injured hippocampus, and how this might contribute to the altered cognition seen in several pathologies common to the hippocampus.