Experimental stroke in the female diabetic, db/db, mouse

Susan J. Vannucci, Lisa B. Willing, Shozo Goto, Nabil J. Alkayed, Robert M. Brucklacher, Teresa L. Wood, Javad Towfighi, Patricia D. Hurn, Ian A. Simpson

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Diabetic hyperglycemia increases brain damage after cerebral ischemia in animals and humans, although the underlying mechanisms remain unclear. Gender-linked differences in ischemic tolerance have been described but have not been studied in the context of diabetes. In the current study, we used a model of unilateral common carotid artery ligation, combined with systemic hypoxia, to study the effects of diabetes and gender on hypoxic-ischemic (HI) brain damage in the genetic model of Type II diabetes, the db/db, mouse. Male and female, control and db/db, mice were subjected to right common carotid artery ligation followed by varying periods of hypoxia (8% oxygen/92% nitrogen) to assess mortality, infarct volume, and tissue damage by light microscopic techniques, Endischemic regional cerebral blood flow (CBF) was determined using [14C] iodoantipyrine autoradiography. Glycolytic and high energy phosphate compounds were measured in blood and brain by enzymatic and fluorometric techniques. Gender and diabetes had significant effects on mortality from HI and extent of brain damage in the survivors. Female mice were more resistant than their male counterparts, such that the severity (mortality and infarction size) in the male diabetics > female diabetics ∼ male controls > female controls. Endischemic CBF and depletion of cerebral high energy reserves were comparable among all groups. Surprisingly, female diabetic mice were more hyperglycemic and demonstrated a greater prolonged lactacidosis than the males; however, they were more resistant to damage. The results suggest a unique pathophysiology of hypoxia-ischemia in the female diabetic brain.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • Brain
  • Cerebral blood flow
  • Diabetes
  • Estrogen
  • Hyperglycemia
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Experimental stroke in the female diabetic, db/db, mouse'. Together they form a unique fingerprint.

  • Cite this

    Vannucci, S. J., Willing, L. B., Goto, S., Alkayed, N. J., Brucklacher, R. M., Wood, T. L., Towfighi, J., Hurn, P. D., & Simpson, I. A. (2001). Experimental stroke in the female diabetic, db/db, mouse. Journal of Cerebral Blood Flow and Metabolism, 21(1), 52-60. https://doi.org/10.1097/00004647-200101000-00007