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

Li, Ping-An; Uchino, Hiroyuki; Elmer, Eskil LU and Siesjö, Bo LU (1997) In Brain Research 753(1). p.133-140
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain damage, Ischemia, Hyperglycemia, Cyclosporin A, Mitochondria, Histopathology, Rat
in
Brain Research
volume
753
issue
1
pages
133 - 140
publisher
Elsevier
external identifiers
  • pmid:9125440
  • scopus:0030951890
ISSN
1872-6240
DOI
10.1016/S0006-8993(97)00005-X
language
English
LU publication?
yes
id
1a32708f-92ae-4591-9346-3e7282dc7a5d (old id 1111489)
date added to LUP
2008-07-17 14:18:01
date last changed
2017-08-06 03:38:06
@article{1a32708f-92ae-4591-9346-3e7282dc7a5d,
  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.},
  author       = {Li, Ping-An and Uchino, Hiroyuki and Elmer, Eskil and Siesjö, Bo},
  issn         = {1872-6240},
  keyword      = {Brain damage,Ischemia,Hyperglycemia,Cyclosporin A,Mitochondria,Histopathology,Rat},
  language     = {eng},
  number       = {1},
  pages        = {133--140},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Amelioration by cyclosporin A of brain damage following 5 or 10 min of ischemia in rats subjected to preischemic hyperglycemia},
  url          = {http://dx.doi.org/10.1016/S0006-8993(97)00005-X},
  volume       = {753},
  year         = {1997},
}