Diazoxide and dimethyl sulphoxide prevent cerebral hypoperfusion-related learning dysfunction and brain damage after carotid artery occlusion

E. Farkas, Ádám Institóris, F. Domoki, A. Mihály, Paul G M Luiten, F. Bari

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Chronic cerebral hypoperfusion, a mild ischemic condition is associated with advancing age and severity of dementia; however, no unanimous therapy has been established to alleviate related neurological symptoms. We imposed a permanent, bilateral occlusion of the common carotid arteries of rats (n=18) to create cerebral hypoperfusion. A mitochondrial ATP-sensitive K+ channel opener diazoxide (DZ, 5 mg/kg) or its solvent dimethyl sulphoxide (DMSO) were administered i.p. (0.25 ml) on five consecutive days after surgery. Sham-operated animals (n=18) served as control for the surgery, while nontreated rats were used as control for the treatments. Three months after the onset of cerebral hypoperfusion, the rats were tested in a hippocampus-related learning paradigm, the Morris water maze. Subsequently, the animals were sacrificed and neurons, astrocytes and microglia were labeled with immunocytochemistry in the dorsal hippocampus. DMSO and diazoxide dissolved in DMSO restored cerebral hypoperfusion-related learning dysfunction and prevented cyclooxygenase-2- positive neuron loss in the dentate gyrus. Cerebral hypoperfusion led to reduced astrocyte proliferation, which was not clearly affected by the treatment. Microglia activation was considerably enhanced by cerebral hypoperfusion, which was completely prevented by diazoxide dissolved in DMSO, but not by DMSO alone. We conclude that diazoxide can moderate ischemia-related neuroinflammation by suppressing microglial activation. Furthermore, we suggest that DMSO is a neuroprotective chemical in ischemic conditions, and it must be considerately used as a solvent for water-insoluble compounds in experimental animal models.

Original languageEnglish
Pages (from-to)252-260
Number of pages9
JournalBrain Research
Volume1008
Issue number2
DOIs
Publication statusPublished - May 22 2004

Fingerprint

Diazoxide
Dimethyl Sulfoxide
Carotid Arteries
Learning
Brain
Microglia
Astrocytes
Hippocampus
Neurons
Water
Common Carotid Artery
Dentate Gyrus
Cyclooxygenase 2
Ambulatory Surgical Procedures
Dementia
Therapeutics
Ischemia
Animal Models
Immunohistochemistry

Keywords

  • Cerebral hypoperfusion
  • Diazoxide
  • Dimethyl sulphoxide
  • Disorders of the nervous system
  • Ischemia
  • Microglia
  • Spatial learning

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Diazoxide and dimethyl sulphoxide prevent cerebral hypoperfusion-related learning dysfunction and brain damage after carotid artery occlusion. / Farkas, E.; Institóris, Ádám; Domoki, F.; Mihály, A.; Luiten, Paul G M; Bari, F.

In: Brain Research, Vol. 1008, No. 2, 22.05.2004, p. 252-260.

Research output: Contribution to journalArticle

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