24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

      review-article
      * ,
      Stroke Research and Treatment
      Hindawi Publishing Corporation

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+)-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

          Related collections

          Most cited references55

          • Record: found
          • Abstract: found
          • Article: not found

          Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury.

          Chronic impairment of forelimb and digit movement is a common problem after stroke that is resistant to therapy. Previous studies have demonstrated that enrichment improves behavioral outcome after focal ischemia; however, postischemic enrichment alone is not capable of enhancing fine digit and forelimb function. Therefore, we combined environmental enrichment with daily skilled-reach training to assess the effect of intensive task-specific rehabilitation on long-term functional outcome. Rats were subjected to either endothelin-1-induced focal ischemia or sham surgery and subsequently designated to enriched-rehabilitation or standard-housing treatment groups starting 15 d after ischemia. Functional assessment of the affected forelimb at 4 and 9 weeks after treatment revealed that ischemic plus enrichment (IE) animals had improved approximately 30% on the staircase-reaching task and were indistinguishable from sham animals for both latency and foot faults in a beam-traversing task. In contrast, ischemic plus standard (IS) animals remained significantly impaired on both tasks. Interestingly, both ischemic groups (IE and IS) relied on the nonaffected forelimb during upright weight-bearing movements, a pattern that persisted for the duration of the experiment. Dendritic arborization of layer V pyramidal cells within the undamaged motor cortex was examined using a Golgi-Cox procedure. IE animals showed enhanced dendritic complexity and length compared with both IS and sham groups. These results suggest that enrichment combined with task-specific rehabilitative therapy is capable of augmenting intrinsic neuronal plasticity within noninjured, functionally connected brain regions, as well as promoting enhanced functional outcome.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Anoxic-ischemic encephalopathy in rats.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model.

              Osteopontin (OPN) is neuroprotective in ischemic brain injuries in adult experimental models; therefore, we hypothesized that OPN would provide neuroprotection and improve long-term neurological function in the immature brain after hypoxic-ischemic (HI) injury. HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O(2) for 2 hours) in postnatal Day 7 rats. OPN (0.03 μg or 0.1 μg) was injected intracerebroventricularly at 1 hour post-HI. Temporal expression of endogenous OPN was evaluated in the normal rat brain at the age of 0, 4, 7, 11, 14, and 21 days and in the ipsilateral hemisphere after HI. The effects of OPN were evaluated using 2-3-5-triphenyl tetrazolium chloride staining, apoptotic cell death assay, and cleaved caspase-3 expression. Neurological function was assessed by the Morris water maze test. Endogenous OPN expression in the brain was the highest at the age of 0 day with continuous reduction until the age of 21 days during development. After HI injury, endogenous OPN expression was increased and peaked at 48 hours. Exogenous OPN decreased infarct volume and improved neurological outcomes 7 weeks after HI injury. OPN-induced neuroprotection was blocked by an integrin antagonist. OPN-induced neuroprotection was associated with cleaved-caspase-3 inhibition and antiapoptotic cell death. OPN treatment improved long-term neurological function against neonatal HI brain injury.
                Bookmark

                Author and article information

                Journal
                Stroke Res Treat
                Stroke Res Treat
                SRT
                Stroke Research and Treatment
                Hindawi Publishing Corporation
                2090-8105
                2042-0056
                2013
                27 February 2013
                : 2013
                : 659374
                Affiliations
                Department of Obstetrics and Gynecology and Center for Perinatal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kiyotake, Kihara, Miyazaki 889-1692, Japan
                Author notes

                Academic Editor: Guodong Cao

                Author information
                https://orcid.org/0000-0003-0158-1663
                Article
                10.1155/2013/659374
                3600180
                23533962
                0d937d2a-083f-4d07-97d5-c57640b81e14
                Copyright © 2013 H. Sameshima and T. Ikenoue.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 October 2012
                : 20 December 2012
                Categories
                Review Article

                Cardiovascular Medicine
                Cardiovascular Medicine

                Comments

                Comment on this article