Ansi Chang1, Maria C.
Smith1,2, Xinghua Yin1,
Robert J. Fox3, Susan M.
Staugaitis1,4 and Bruce D.
1Department of Neurosciences, Lerner Research
Institute, 2Department of Neurosciences, Case Western Reserve
University, School of Medicine, 3Mellen Center for Multiple Sclerosis
and 4Department of Anatomic Pathology, Cleveland Clinic, Cleveland,
Correspondence to: Bruce D. Trapp, Department of Neurosciences, Lerner
Research Institute, Cleveland Clinic, 9500 Euclid Avenue NC30, Cleveland, OH
44195, USA E-mail: email@example.com
Subcortical white matter in the adult human brain contains a
population of interneurons that helps regulate cerebral blood
flow. We investigated the fate of these neurons following subcortical
white matter demyelination. Immunohistochemistry was used to
examine neurons in normal-appearing subcortical white matter
and seven acute and 59 chronic demyelinated lesions in brains
from nine patients with multiple sclerosis and four controls.
Seven acute and 44 of 59 chronic multiple sclerosis lesions had
marked neuronal loss. Compared to surrounding normal-appearing white
matter, the remaining 15 chronic multiple sclerosis lesions contained
a 72% increase in mature interneuron density, increased synaptic
densities and cells with phenotypic characteristics of immature
neurons. Lesion areas with increased neuron densities contained a
morphologically distinct population of activated microglia.
Subventricular zones contiguous with demyelinated lesions also
contained an increase in cells with phenotypes of neuronal
precursors. These results support neurogenesis in a subpopulation of
demyelinated subcortical white matter lesions in multiple sclerosis
Key Words: multiple sclerosis; white matter neurons;
Abbreviations: DAB, diaminobenzidine; MAP2,
microtubule-associated protein 2; MHC, major histocompatibility complex; nNOS,
neuronal nitric oxide synthase; NPY, neuropeptide Y; PLP, proteolipid protein;
SVZ, subventricular zone
Received March 18, 2008. Revised June 10,
2008. Accepted June 25, 2008.