Propagation of spreading depression inversely correlates with cortical myelin content.
OBJECTIVE
Cortical myelin can be severely affected in patients with demyelinating disorders of the central nervous system. However, the functional implication of cortical demyelination remains elusive. In this study, we investigated whether cortical myelin influences cortical spreading depression (CSD).


METHODS
CSD measurements were performed in rodent models of toxic and autoimmune induced cortical demyelination, in neuregulin-1 type I transgenic mice displaying cortical hypermyelination, and in glial fibrillary acidic protein-transgenic mice exhibiting pronounced astrogliosis.


RESULTS
Cortical demyelination, but not astrogliosis or inflammation per se, was associated with accelerated CSD. In contrast, hypermyelinated neuregulin-1 type I transgenic mice displayed a decelerated CSD propagation.


CONCLUSIONS
Cortical myelin may be crucially involved in the stabilization and buffering of extracellular ion content that is decisive for CSD propagation velocity and cortical excitability, respectively. Our data thus indicate that cortical involvement in human demyelinating diseases may lead to relevant alterations of cortical function.
Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany. merkler@med.uni-goettingen.de
Doron
D
Merkler
Florian
F
Klinker
Tanja
T
Jürgens
Raoul
R
Glaser
Walter
W
Paulus
Bastian G
BG
Brinkmann
Michael W
MW
Sereda
Christine
C
Stadelmann-Nessler
Rubem C A
RC
Guedes
Wolfgang
W
Brück
David
D
Liebetanz
D000818:Animals; D001253:Astrocytes; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D004569:Electroencephalography; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005911:Gliosis; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000032:analysis* / Q000502:physiology; D009186:Myelin Sheath / Q000235:genetics / Q000502:physiology*; D020890:Neuregulin-1 / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew
D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D020890:Neuregulin-1; D003471:Cuprizone