Pharmacologic amelioration of severe hypoglycemia-induced neuronal damage

Julie M. Silverstein, Daniel Musikantow, Erwin C. Puente, Dorit Daphna-Iken, Adam J. Bree, Simon J. Fisher

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Hypoglycemia is a common complication for insulin treated people with diabetes. Severe hypoglycemia, which occurs in the setting of excess or ill-timed insulin administration, has been shown to cause brain damage. Previous pre-clinical studies have shown that memantine (an N-methyl-d-aspartate receptor antagonist) and erythropoietin can be neuroprotective in other models of brain injury. We hypothesized that these agents might also be neuroprotective in reponse to severe hypoglycemia-induced brain damage. To test this hypothesis, 9-week old, awake, male Sprague-Dawley rats underwent hyperinsulinemic (0.2Ukg -1min -1) hypoglycemic clamps to induce severe hypoglycemia (blood glucose 10-15mg/dl for 90min). Animals were randomized into control (vehicle) or pharmacological treatments (memantine or erythropoietin). One week after severe hypoglycemia, neuronal damage was assessed by Fluoro-Jade B and hematoxylin and eosin staining of brain sections. Treatment with both memantine and erythropoietin significantly decreased severe hypoglycemia-induced neuronal damage in the cortex by 35% and 39%, respectively (both p<0.05 vs. controls). These findings demonstrate that memantine and erythropoietin provide a protective effect against severe hypoglycemia-induced neuronal damage.

Original languageEnglish
Pages (from-to)23-28
Number of pages6
JournalNeuroscience Letters
Issue number1
StatePublished - Mar 29 2011


  • Cortex
  • Erythropoietin
  • Hippocampus
  • Insulin
  • Memantine


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