i(3)so3-galactosylceramide and Brain-Ischemia

Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Chromatography, Liquid; Chronic Disease; Dementia, Vascular; Female; Gray Matter; Humans; Lysophospholipids; Male; Mass Spectrometry; Monoglycerides; Phospholipids; Sphingolipids; Sulfoglycosphingolipids; Temporal Lobe; White Matter

ATP was entrapped inside negatively charged liposomes composed of sulfatide, in order to improve its penetration into the brain and to reduce its degradation into other tissues. These liposomes were prepared according to an original method allowing a satisfying stability of the formulation. Liposomally entrapped ATP was administered intracerebroventricularly to rats submitted to brain ischemic episodes by both carotid artery clamping and systemic blood pressure lowering (during 3 minutes every 15 minutes). Such treatment importantly increases the number of ischemic episodes before brain silence appeared. So, this paper allows new perspectives in the administration of drugs into the brain.

Topics: Adenosine Triphosphate; Animals; Biological Availability; Brain Ischemia; Injections, Intraventricular; Liposomes; Male; Rats; Rats, Inbred Strains; Sulfoglycosphingolipids