Disease relevance of Brain Ischemia

• Damage to neurons caused by focal cerebral ischemia and epileptic seizures was exacerbated in TNFR-KO mice, indicating that TNF serves a neuroprotective function [1].
• Thus, COX-2 is transiently induced after SD and focal ischemia by activation of N-methyl-D-aspartic acid-receptors and PLA2, most prominently in cortical neurons that are at a high risk to die after focal brain ischemia [2].
• This spectrum of pharmacologic activity suggests that TA-3090 would selectively block Ca2+ entry into cerebrovascular smooth muscle through potential-sensitive and receptor-operated Ca2+ channels that would be expected to increase in subarachnoid hemorrhage and cerebral ischemia [3].
• Diarylguanidines are structurally unrelated to known blockers of NMDA channels and, therefore, represent a new compound series for the development of neuroprotective agents with therapeutic value in patients suffering from stroke, from brain or spinal cord trauma, from hypoglycemia, and possibly from brain ischemia due to heart attack [4].
• Inducible NOS in glia may, by generating nitric oxide, contribute to the neuronal damage associated with cerebral ischemia and/or demyelinating diseases [5].

Psychiatry related information on Brain Ischemia

• Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate produces both energy depletion and striatal lesions similar to that seen in cerebral ischemia and Huntington's disease [6].
• These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems [7].
• Citicoline is a neuroprotective agent used clinically to treat for instance Parkinson disease, stroke, Alzheimer's disease and brain ischemia [8].
• It has been shown that dysfunction of the cholinergic neuronal system plays an important role in memory loss and that bifemelane induces recovery of reduced cerebral cholinergic neuronal activity associated with brain ischemia or aging [9].
• Treatment with steroid resulted in prompt resolution of visual hallucinations, despite persistent visual loss, suggesting that cerebral ischemia is a cofactor for the development of CBS [10].

High impact information on Brain Ischemia

• In brain ischemia, gating of postsynaptic glutamate receptors is thought to initiate Ca2+ overload leading to excitotoxic neuronal death [11].
• The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury [12].
• Therapeutic use of magnesium sulfate in selected cases of cerebral ischemia and seizure [13].
• Inactivation of the adenosine A(2A) receptor (A(2A)R) consistently protects against ischemic brain injury and other neural insults, but the relative contribution of A(2A)Rs on peripheral inflammatory cells versus A(2A)Rs expressed on neurons and glia is unknown [14].
• MMP-9 levels were lower in tPA knockouts compared with wild-type mice after focal cerebral ischemia [15].

Chemical compound and disease context of Brain Ischemia

• Thus, under conditions that lead to lactate accumulation (cerebral ischemia) this "end product" may be a useful alternative as a substrate for energy metabolism [16].
• DATA SYNTHESIS: Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition: promotion of cholinergic and serotonergic activity in specific brain regions, maintenance of neural circuitry, favorable lipoprotein alterations, and prevention of cerebral ischemia [17].
• Estrogen seems more effective as a prophylactic treatment in females at risk for cardiac and ischemic brain injury, whereas progesterone appears to be more helpful in the post-injury treatment of both male and female subjects with acute traumatic brain damage [18].
• Considered together, these results indicate that polyamine oxidase-derived 3-aminopropanal is a mediator of the brain damaging sequelae of cerebral ischemia, which can be therapeutically modulated [19].
• Increased Ca2+ influx through activated N-methyl-D-aspartate (NMDA) receptors and voltage-dependent Ca2+ channels (VDCC) is a major determinant of cell injury following brain ischemia [20].

Biological context of Brain Ischemia

• Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis [21].
• We report that disruption of Rho-mediated endothelial actin cytoskeleton leads to the upregulation of eNOS expression and reduces the severity of cerebral ischemia following MCA occlusion [22].
• BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia [23].
• Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease [24]?
• These findings suggest that derangement of cyclic AMP-related intracellular signal transduction closely parallels ischemic neuronal damage and that persistent enhancement of this signaling pathway is important for neuronal survival in acute cerebral ischemia [25].

Anatomical context of Brain Ischemia

• Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury [14].
• Release of IL-6 from astrocytes could exert a paracrine neurotrophic effect in brain ischemia [26].
• Intravenous administration of 3alpha5betaHS to rats (at a nonsedating dose) following focal cerebral ischemia induced by middle cerebral artery occlusion significantly reduces cortical and subcortical infarct size [27].
• We found that APP751 mice have higher activity of p38 mitogen-activated protein kinase (p38 MAPK) in microglia, the main immune effector cells within the brain, and increased vulnerability to brain ischemia when compared with age-matched wild-type mice [28].
• Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia [23].

Gene context of Brain Ischemia

• This potential role is further highlighted by the recent findings that the expression of ER-alpha and ER-beta changes following ischemic brain injury and that these changes correlate with the hormonal modulation of protective factors [29].
• Here we show that the MEK/ERK pathway is activated during focal cerebral ischemia and may play a role in inducing damage [30].
• Previous studies have shown that caspase-1 knockout (KO) mice and transgenic mice expressing a dominant-negative caspase-1 construct are resistant to ischemic brain injury [31].
• Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation [32].
• Effects of cerebral ischemia in mice deficient in Persephin [33].

Analytical, diagnostic and therapeutic context of Brain Ischemia

• We show that NEPPs are neuroprotective both in vitro from glutamate-related excitotoxicity and in vivo in a model of cerebral ischemia/reperfusion injury (stroke) [34].
• In this study, we fused the protein transduction domain (PTD) of the HIVTat protein to FNK and used the construct in an animal model of ischemic brain injury [35].
• To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family [36].
• Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography [37].
• Protein transduction domains (PTDs), such as the TAT PTD, have been shown to deliver a wide variety of cargo in cell culture and to treat preclinical models of cancer and cerebral ischemia [38].

References