Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Wld(s) mouse mutant demonstrates a remarkable phenotype of delayed axonal and synaptic degeneration after nerve lesion. In this study, the authors tested the hypothesis that expression of Wld protein is neuroprotective in an in vivo mouse model of global cerebral ischemia. This model is associated with selective neuronal degeneration in specific brain regions such as the caudate nucleus and CA2 hippocampal pyramidal cell layer. The extent of neuronal damage was quantified in Wld(s) compared to wild-type mice after an identical episode of global cerebral ischemia. The results demonstrated a significant and marked reduction in the extent of neuronal damage in Wld(s) as compared to wild-type C57Bl/6 mice. In the caudate nucleus, Wld expression significantly reduced the percentage of ischemic neuronal damage after global ischemia (Wld(s), 27.7 +/- 16.8%; wild-type mice, 58.7 +/- 32.3%; P = 0.036). Similarly, in the CA2 pyramidal cell layer, there was a significant reduction of neuronal damage in the Wld(s) mice as compared to wild-type mice after ischemia (Wld(s), 17.7 +/- 23.0%; wild-type mice, 41.9 +/- 28.0%; P < 0.023). Thus, these results clearly demonstrate that the Wld gene confers substantial neuroprotection after cerebral ischemia, and suggest a new role to that previously described for Wld(s).
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PMID:Neuroprotection after transient global cerebral ischemia in Wld(s) mutant mice. 1468 17

Microglia play an important role as immune cells in the central nervous system (CNS). Microglia are activated in threatened physiological homeostasis, including CNS trauma, apoptosis, ischemia, inflammation, and infection. Activated microglia show a stereotypic, progressive series of changes in morphology, gene expression, function, and number and produce and release various chemical mediators, including proinflammatory cytokines that can produce immunological actions and can also act on neurons to alter their function. Recently, a great deal of attention is focusing on the relation between activated microglia through adenosine 5'-triphosphate (ATP) receptors and neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes, or infection. This type of pain can be so severe that even light touching can be intensely painful and it is generally resistant to currently available treatments. There is abundant evidence that extracellular ATP and microglia have an important role in neuropathic pain. The expression of P2X4 receptor, a subtype of ATP receptors, is enhanced in spinal microglia after peripheral nerve injury model, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain. Several cytokines such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in the dorsal horn are increased after nerve lesion and have been implicated in contributing to nerve-injury pain, presumably by altering synaptic transmission in the CNS, including the spinal cord. Nerve injury also leads to persistent activation of p38 mitogen-activated protein kinase (MAPK) in microglia. An inhibitor of this enzyme reverses mechanical allodynia following spinal nerve ligation (SNL). ATP is able to activate MAPK, leading to the release of bioactive substances, including cytokines, from microglia. Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain. Understanding the key roles of ATP receptors, including P2X4 receptors, in the microglia may lead to new strategies for the management of neuropathic pain.
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PMID:The function of microglia through purinergic receptors: neuropathic pain and cytokine release. 1616 95

Peripheral nerves are essential connections between the central nervous system and muscles, autonomic structures and sensory organs. Their injury is one of the major causes for severe and longstanding impairment in limb function. Acute peripheral nerve lesion has an important inflammatory component and is considered as ischemia-reperfusion (IR) injury. Surgical repair has been the standard of care in peripheral nerve lesion. It has reached optimal technical development but the end results still remain unpredictable and complete functional recovery is rare. Nevertheless, nerve repair is not primarily a mechanical problem and microsurgery is not the only key to success. Lately, there have been efforts to develop alternatives to nerve graft. Work has been carried out in basal lamina scaffolds, biologic and non-biologic structures in combination with neurotrophic factors and/or Schwann cells, tissues, immunosuppressive agents, growth factors, cell transplantation, principles of artificial sensory function, gene technology, gangliosides, implantation of microchips, hormones, electromagnetic fields and hyperbaric oxygenation (HBO). HBO appears to be a beneficial adjunctive treatment for surgical repair in the acute peripheral nerve lesion, when used at lower pressures and in a timely fashion (<6 hours).
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PMID:Hyperbaric oxygenation in peripheral nerve repair and regeneration. 1743 3

Microglia is activated by brain injury. They migrate in response to ATP and although adenosine alone has no effect on wild type microglial migration, we show that inhibition of adenosine receptors impedes ATP triggered migration. CD39 is the dominant cellular ectonucleotidase that degrades nucleotides to nucleosides, including adenosine. Importantly, ATP fails to stimulate P2 receptor mediated migration in cd39(-/-) microglia. However, the effects of ATP on migration in cd39(-/-) microglia can be restored by co-stimulation with adenosine or by addition of a soluble ectonucleotidase. We also tested the impact of cd39-deletion in a model of ischemia, in an entorhinal cortex lesion and in the facial nucleus after facial nerve lesion. The accumulation of microglia at the pathological sites was markedly decreased in cd39(-/-) animals. We conclude that the co-stimulation of purinergic and adenosine receptors is a requirement for microglial migration and that the expression of cd39 controls the ATP/adenosine balance.
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PMID:The ectonucleotidase cd39/ENTPDase1 modulates purinergic-mediated microglial migration. 1809 26


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