Blood Glutamate Scavenger as a Novel Neuroprotective Treatment in Spinal Cord Injury
| Autor: | Angela Ruban, Shira Solomon, Ronit Pinkas-Kramarski, Yona Goldshmit, Eran Schmukler, Ghil Jona |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Excitotoxicity Glutamic Acid Inflammation Pharmacology medicine.disease_cause Neuroprotection Glial scar 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Cytotoxicity Spinal cord injury Spinal Cord Injuries business.industry Glutamate receptor medicine.disease Scavenger (chemistry) Recombinant Proteins Mice Inbred C57BL 030104 developmental biology Neuroprotective Agents nervous system Female Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Aspartate Aminotransferase Cytoplasmic |
| Zdroj: | Journal of neurotrauma. 35(21) |
| ISSN: | 1557-9042 |
| Popis: | Neurotrauma causes immediate elevation of extracellular glutamate (Glu) levels, which creates excitotoxicity and facilitates inflammation, glial scar formation, and consequently neuronal death. Finding factors that reduce the inflammatory response and glial scar formation, and increase neuronal survival and neurite outgrowth, are of major importance for improving the outcome after spinal cord injury (SCI). In the present study, we evaluated a new treatment aiming to remove central nervous system (CNS) Glu into the systemic blood circulation by intravenous (IV) administration of blood Glu scavengers (BGS) such as the enzyme recombinant glutamate-oxaloacetate transaminase 1 (rGOT1) and its co-substrate. In this study we induced in mice an SCI (hemisection), and 1 h post-injury started administering BGS treatment for 5 consecutive days. The treatment reduced the expression levels of p-p38, which regulates apoptosis and increased the expression of p-Akt, which mediates cell survival. Moreover, this treatment decreased pro-inflammatory cytokine expression and microglia activation, reduced astrocytes' reactivity, and facilitated expression of radial glia markers such as Pax6 and nestin. BGS treatment increased the survival of neurons at lesion site and enabled axonal regeneration into the injury site. These effects were correlated with improved functional recovery of the left paretic hindlimb. Thus, early pharmacological intervention with BGS following SCI may be neuroprotective and create a pro-regenerative environment by modulating glia cell response. In light of our results, the availability of the method to remove excess Glu from CNS without the need to deliver drugs across the blood-brain barrier (BBB) and with minimal or no adverse effects may provide a major therapeutic asset. |
| Databáze: | OpenAIRE |
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