Prevention of hypoglycemia-induced neuronal death by minocycline

Seok J. Won, Jin H. Kim, Byung H. Yoo, Min Sohn, Tiina M. Kauppinen, Man-Seong Park, Hyung Joo Kwon, Jialing Liu, Sang W. Suh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients.

Original languageEnglish
Article number225
JournalJournal of Neuroinflammation
Volume9
DOIs
Publication statusPublished - 2012 Sep 22
Externally publishedYes

Fingerprint

Minocycline
Hypoglycemia
Animal Models
Neuroprotective Agents
Tetracycline
Brain Injuries
Peroxidase
Reperfusion
Blood Glucose

Keywords

  • Hypoglycemia
  • Microglia
  • Minocycline
  • Neuronal death

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Won, S. J., Kim, J. H., Yoo, B. H., Sohn, M., Kauppinen, T. M., Park, M-S., ... Suh, S. W. (2012). Prevention of hypoglycemia-induced neuronal death by minocycline. Journal of Neuroinflammation, 9, [225]. https://doi.org/10.1186/1742-2094-9-225

Prevention of hypoglycemia-induced neuronal death by minocycline. / Won, Seok J.; Kim, Jin H.; Yoo, Byung H.; Sohn, Min; Kauppinen, Tiina M.; Park, Man-Seong; Kwon, Hyung Joo; Liu, Jialing; Suh, Sang W.

In: Journal of Neuroinflammation, Vol. 9, 225, 22.09.2012.

Research output: Contribution to journalArticle

Won, SJ, Kim, JH, Yoo, BH, Sohn, M, Kauppinen, TM, Park, M-S, Kwon, HJ, Liu, J & Suh, SW 2012, 'Prevention of hypoglycemia-induced neuronal death by minocycline', Journal of Neuroinflammation, vol. 9, 225. https://doi.org/10.1186/1742-2094-9-225
Won, Seok J. ; Kim, Jin H. ; Yoo, Byung H. ; Sohn, Min ; Kauppinen, Tiina M. ; Park, Man-Seong ; Kwon, Hyung Joo ; Liu, Jialing ; Suh, Sang W. / Prevention of hypoglycemia-induced neuronal death by minocycline. In: Journal of Neuroinflammation. 2012 ; Vol. 9.
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