Dendritic alterations after dynamic axonal stretch injury in vitro.
Traumatic axonal injury (TAI) is the most common and important pathology of traumatic brain injury (TBI). However, little is known about potential indirect effects of TAI on dendrites. In this study, we used a well-established in vitro model of axonal stretch injury to investigate TAI-induced changes in dendrite morphology. Axons bridging two separated rat cortical neuron populations plated on a deformable substrate were used to create a zone of isolated stretch injury to axons. Following injury, we observed the formation of dendritic alterations or beading along the dendrite shaft. Dendritic beading formed within minutes after stretch then subsided over time. Pharmacological experiments revealed a sodium-dependent mechanism, while removing extracellular calcium exacerbated TAI's effect on dendrites. In addition, blocking ionotropic glutamate receptors with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevented dendritic beading. These results demonstrate that axon mechanical injury directly affects dendrite morphology, highlighting an important bystander effect of TAI. The data also imply that TAI may alter dendrite structure and plasticity in vivo. An understanding of TAI's effect on dendrites is important since proper dendrite function is crucial for normal brain function and recovery after injury.
Monnerie
Hubert
H
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19107, USA.
Tang-Schomer
Min D
MD
Iwata
Akira
A
Smith
Douglas H
DH
Kim
Haesun A
HA
Le Roux
Peter D
PD
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure*; D001930:Brain Injuries / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000648:ultrastructure*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D019579:Neocortex / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012964:Sodium / Q000502:physiology; D013314:Stress, Mechanical
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D012964:Sodium; D002118:Calcium