Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy : Nature Medicine : Nature Publishing Group

Previous attempts to identify neuroprotective targets by studying the ischemic cascade and devising ways to suppress it have failed to translate to efficacious therapies for acute ischemic stroke. We hypothesized that studying the molecular determinants of endogenous neuroprotection in two well-established paradigms, the resistance of CA3 hippocampal neurons to global ischemia and the tolerance conferred by ischemic preconditioning (IPC), would reveal new neuroprotective targets. We found that the product of the tuberous sclerosis complex 1 gene (TSC1), hamartin, is selectively induced by ischemia in hippocampal CA3 neurons. In CA1 neurons, hamartin was unaffected by ischemia but was upregulated by IPC preceding ischemia, which protects the otherwise vulnerable CA1 cells. Suppression of hamartin expression with TSC1 shRNA viral vectors both in vitro and in vivo increased the vulnerability of neurons to cell death following oxygen glucose deprivation (OGD) and ischemia. In vivo, suppression of TSC1 expression increased locomotor activity and decreased habituation in a hippocampal-dependent task. Overexpression of hamartin increased resistance to OGD by inducing productive autophagy through an mTORC1-dependent mechanism.

Olive oil component alleviates intestinal ischemia and reperfusion

 "Here's another reason why you should include olive oil in your diet: A new research report published in the Journal of Leukocyte Biology suggests that at least one compound in olive oil significantly reduces intestinal ischemia (restricted blood supply) and the resulting reperfusion injury (tissue damage caused when blood supply returns). The compound, called "oleuropein aglycone," is the most prominent polyphenol found in olive oil and could become a novel therapeutic target aimed at treating intestinal ischemia and reperfusion injury in humans. Ultimately, this research could lead to therapeutic benefits for patients with spinal cord injuries, arthritis and pleurisy, as well as those suffering from intestinal ischemia/reperfusion."

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Molecular Psychiatry - An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

Investigating and understanding gene–environment interaction (G × E) in a neurodevelopmentally and biologically plausible manner is a major challenge for schizophrenia research. Hypoxia during neurodevelopment is one of several environmental factors related to the risk of schizophrenia, and links between schizophrenia candidate genes and hypoxia regulation or vascular expression have been proposed. Given the availability of a wealth of complex genetic information on schizophrenia in the literature without knowledge on the connections to environmental factors, we now systematically collected genes from candidate studies (using SzGene), genome-wide association studies (GWAS) and copy number variation (CNV) analyses, and then applied four criteria to test for a (theoretical) link to ischemia–hypoxia and/or vascular factors. In all, 55% of the schizophrenia candidate genes (n=42 genes) met the criteria for a link to ischemia–hypoxia and/or vascular factors. Genes associated with schizophrenia showed a significant, threefold enrichment among genes that were derived from microarray studies of the ischemia–hypoxia response (IHR) in the brain. Thus, the finding of a considerable match between genes associated with the risk of schizophrenia and IHR and/or vascular factors is reproducible. An additional survey of genes identified by GWAS and CNV analyses suggested novel genes that match the criteria. Findings for interactions between specific variants of genes proposed to be IHR and/or vascular factors with obstetric complications in patients with schizophrenia have been reported in the literature. Therefore, the extended gene set defined here may form a reasonable and evidence-based starting point for hypothesis-based testing of G × E interactions in clinical genetic and translational neuroscience studies.