QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kharlamov, A. Articles by Armstrong, D. Search for Related Content PubMed PubMed Citation Articles by Kharlamov, A. Articles by Armstrong, D.

 Previous Article  |  Next Article 

Journal of Neuroscience, Vol 13, 2483-2494, Copyright © 1993 by Society for Neuroscience

ARTICLE

Semisynthetic sphingolipids prevent protein kinase C translocation and neuronal damage in the perifocal area following a photochemically induced thrombotic brain cortical lesion

A Kharlamov, A Guidotti, E Costa, R Hayes and D Armstrong
Fidia-Georgetown Institute for the Neurosciences, Georgetown University, School of Medicine, Washington, D.C. 20007.

A vascular thrombotic lesion localized to the rat sensorimotor cortex was produced following intravenous injection of the photosensitive dye rose bengal, and its activation with a small beam of high-intensity white light focused to the skull overlaying the sensorimotor cortex. In the sensorimotor cortex at various times after the triggering event, two contiguous brain regions with different degree(s) of neuronal damage can be distinguished: (1) a primary thrombotic ischemic core where the majority of cells are dead and (2) a penumbra region surrounding the core lesion in which a slower progressive neuronal degeneration is occurring. Importantly, in both brain regions the neuronal degeneration is associated with the activation and persistent translocation of protein kinase C (PKC) as indicated by an increase in 4-beta-3H-phorbol-12,13-dibutyrate (3H-PDBu) binding. Moreover, the demonstration that in the area penumbra the neuronal degeneration and the persistent translocation of PKC can be inhibited by a pretreatment with dizocilpine (i.e., MK-801) indicates that the dynamics of the progression of the neuronal degeneration are maintained by glutamate accumulating in the extraneuronal fluids. MK-801 additionally prevents the transcriptional activation of several immediate-early genes (IEGs) (e.g., c-fos) and their cognate third nuclear messenger (i.e., c-Fos) expression present in the hemisphere ipsilateral to the lesion. On the other hand, LIGA4 and LIGA20 derivatives of GM1 lysoganglioside reduce the membrane translocation of PKC and the neuronal damage in the penumbra area, but fail to change the increase of IEG expression in the cortex ipsilateral to the lesion.

This article has been cited by other articles:

				R. Bright and D. Mochly-Rosen The Role of Protein Kinase C in Cerebral Ischemic and Reperfusion Injury Stroke, December 1, 2005; 36(12): 2781 - 2790. [Abstract] [Full Text] [PDF]

				T. Nakagawa, A. Morotomi, M. Tani, N. Sueyoshi, H. Komori, and M. Ito C18:3-GM1a induces apoptosis in Neuro2a cells: enzymatic remodeling of fatty acyl chains of glycosphingolipids J. Lipid Res., June 1, 2005; 46(6): 1103 - 1112. [Abstract] [Full Text] [PDF]

				A. Kharlamov, E. Kharlamov, and D. M. Armstrong Age-Dependent Increase in Infarct Volume Following Photochemically Induced Cerebral Infarction: Putative Role of Astroglia J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2000; 55(3): 135B - 141. [Abstract] [Full Text]

				S. Miettinen, R. Roivainen, R. Keinanen, T. Hokfelt, and J. Koistinaho Specific Induction of Protein Kinase Cdelta Subspecies after Transient Middle Cerebral Artery Occlusion in the Rat Brain: Inhibition by MK-801 J. Neurosci., October 1, 1996; 16(19): 6236 - 6245. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help