The Matrix Receptor CD44 Is Present in Astrocytes throughout the Human Central Nervous System and Accumulates in Hypoxia and Seizures
Osama Al-Dalahmah,
Alexander A. Sosunov,
Yu Sun,
Yang Liu,
Nacoya Madden,
E. Sander Connolly,
Carol M. Troy,
Guy M. McKhann,
James E. Goldman
Affiliations
Osama Al-Dalahmah
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
Alexander A. Sosunov
Department of Neurosurgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
Yu Sun
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
Yang Liu
Department of Pathology, Albany Medical Center, Albany, NY 12208, USA
Nacoya Madden
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
E. Sander Connolly
Department of Neurosurgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
Carol M. Troy
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
Guy M. McKhann
Department of Neurosurgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
James E. Goldman
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA
In the mammalian isocortex, CD44, a cell surface receptor for extracellular matrix molecules, is present in pial-based and fibrous astrocytes of white matter but not in protoplasmic astrocytes. In the hominid isocortex, CD44+ astrocytes comprise the subpial “interlaminar” astrocytes, sending long processes into the cortex. The hippocampus also contains similar astrocytes. We have examined all levels of the human central nervous system and found CD44+ astrocytes in every region. Astrocytes in white matter and astrocytes that interact with large blood vessels but not with capillaries in gray matter are CD44+, the latter extending long processes into the parenchyma. Motor neurons in the brainstem and spinal cord, such as oculomotor, facial, hypoglossal, and in the anterior horn of the spinal cord, are surrounded by CD44+ processes, contrasting with neurons in the cortex, basal ganglia, and thalamus. We found CD44+ processes that intercalate between ependymal cells to reach the ventricle. We also found CD44+ astrocytes in the molecular layer of the cerebellar cortex. Protoplasmic astrocytes, which do not normally contain CD44, acquire it in pathologies like hypoxia and seizures. The pervasive and inducible expression of CD44 in astrocytes is a novel finding that lays the foundations for functional studies into the significance of CD44 in health and disease.