Amelioration by cyclosporin A of brain damage following 5 or 10 min of ischemia in rats subjected to preischemic hyperglycemia

Research output: Contribution to journalArticle

Abstract

It has recently been shown that the immunosuppressant cyclosporin A (CsA) dramatically ameliorates the selective neuronal necrosis which results from 10 min of forebrain ischemia in rats. Since CsA is a virtually specific blocker of the mitochondrial permeability transition (MPT) pore which is assembled under adverse conditions, such as mitochondrial calcium accumulation and oxidative stress, the results suggest that the delayed neuronal death is due to an MPT. In the present study we explored whether CsA can also ameliorate the aggravated brain damage which is observed in hyperglycemic subjects, and which encompasses rapidly evolving neuronal lesions, edema, and postischemic seizures. Anaesthetised rats with a plasma glucose concentration of approximately 13 mM were subjected to 10 min of forebrain ischemia, and allowed a recovery period of 7 days. In these animals, CsA prevented seizure from occurring and virtually eliminated neuronal necrosis. In order to allow even higher plasma glucose values (approximately 20 mM) to be studied, with long-term recovery, the duration of ischemia had to be reduced to 5 min. Again, CsA suppressed seizure activity and reduced neuronal damage. However, the effects were not as marked or consistent as in the 10 min group, suggesting that excessive tissue acidosis recruits mechanisms of damage which are not sensitive to CsA.

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Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Brain damage, Ischemia, Hyperglycemia, Cyclosporin A, Mitochondria, Histopathology, Rat
Original languageEnglish
Pages (from-to)133-140
JournalBrain Research
Volume753
Issue number1
Publication statusPublished - 1997
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurology, Lund (013027000), Laboratory for Experimental Brain Research (013041000)