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One critical factor is the survival of motoneurons, which are very vulnerable cells. To clarify the early pathophysiological mechanisms of spinal damage, an <jats:italic>in\u00a0vitro<\/jats:italic> injury model of the rat spinal cord caused by moderate excitotoxicity was used. With this preparation we investigated whether motoneuron survival was dependent on the expression of the neuroprotective protein <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70. In the present study excitotoxicity evoked by kainate induced delayed (24\u00a0h) loss (35%) of motoneurons, which became pyknotic with translocation of the cell death biomarker apoptosis\u2010inducing factor (<jats:styled-content style=\"fixed-case\">AIF<\/jats:styled-content>) to the nucleus. This process was concomitant with suppression of locomotor network electrical activity. Surviving cells showed strong expression of <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 without nuclear <jats:styled-content style=\"fixed-case\">AIF<\/jats:styled-content>. The <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 inhibitor <jats:styled-content style=\"fixed-case\">VER<\/jats:styled-content>155008 <jats:italic>per se<\/jats:italic> induced neurotoxicity similar to that of kainate, while the <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>90 inhibitor geldanamycin did not damage spinal tissue. Electrophysiological recording following kainate or <jats:styled-content style=\"fixed-case\">VER<\/jats:styled-content>155008 indicated depression of motoneuron field potentials, with decreased excitability and impaired synaptic transmission. When these two drugs were applied together, more intense neurotoxicity emerged. Our data indicate that <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 was one important contributor to motoneuron survival and suggest that enhancing <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 activity is a potential future strategy for neuroprotecting these cells.<\/jats:p>","DOI":"10.1111\/ejn.13108","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T08:38:55Z","timestamp":1445503135000},"page":"3054-3065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Role of HSP70 in motoneuron survival after excitotoxic stress in a rat spinal cord injury model <i>in\u00a0vitro<\/i>"],"prefix":"10.1111","volume":"42","author":[{"given":"Ayisha","family":"Shabbir","sequence":"first","affiliation":[{"name":"Neuroscience Department Scuola Internazionale Superiore di Studi Avanzati (SISSA) Via Bonomea 265 34136 Trieste 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