Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane

• Published in: PloS one Vol. 7; no. 7; p. e41090
• Main Authors: Porritt, Michelle J, Andersson, Helene C, Hou, Linda, Nilsson, Åsa, Pekna, Marcela, Pekny, Milos, Nilsson, Michael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.07.2012; Public Library of Science (PLoS)
• Subjects: acute ischemic-stroke; Adhesion tests; Analysis; Animals; Antioxidants; Antioxidants (Nutrients); Biology; Brain; Cerebral cortex; Cerebral infarction; Cerebral Infarction - genetics; Cerebral Infarction - metabolism; Cerebral Infarction - pathology; Cylinders; damage; Disease Models, Animal; DNA repair; Enzymes; Gene expression; Gene Expression Regulation - drug effects; Genes; Glial cells; Gliosis; induction; Infarction; injury; Ischemia; Isothiocyanates; Kinases; Male; Medicine; Mice; Motor Activity - drug effects; NAD(P)H Dehydrogenase (Quinone) - genetics; NAD(P)H Dehydrogenase (Quinone) - metabolism; Neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neurosciences; Neurovetenskaper; NF-E2-Related Factor 2 - agonists; NF-E2-Related Factor 2 - metabolism; NRF2 protein; oxidoreductase-1; Physiology; Prevention; protection; Proteins; rat; Rehabilitation; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Stroke; Sulforafan; Sulforaphane; Sulfoxides; Thiocyanates - administration & dosage; Thiocyanates - pharmacology; Transcription (Genetics); Transcription activation; transcription factor nrf2; Transcription factors; Walking
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041090

Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p.) after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage.